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EARLY AND LATE STAGE PROFILES FOR A CHEMOTAXIS MODEL WITH DENSITY-DEPENDENT JUMP PROBABILITY

  • In this paper, we derive a chemotaxis model with degenerate diffusion and density-dependent chemotactic sensitivity, and we provide a more realistic description of cell migration process for its early and late stages. Different from the existing studies focusing on the case of non-degenerate diffusion, this model with degenerate diffusion causes us some essential difficulty on the boundedness estimates and the propagation behavior of its compact support. In the presence of logistic damping, for the early stage before tumour cells spread to the whole domain, we first estimate the expanding speed of tumour region as O(tβ) for 0<β<12 . Then, for the late stage of cell migration, we further prove that the asymptotic profile of the original system is just its corresponding steady state. The global convergence of the original weak solution to the steady state with exponential rate O(ect) for some c>0 is also obtained.

    Citation: Tianyuan Xu, Shanming Ji, Chunhua Jin, Ming Mei, Jingxue Yin. EARLY AND LATE STAGE PROFILES FOR A CHEMOTAXIS MODEL WITH DENSITY-DEPENDENT JUMP PROBABILITY[J]. Mathematical Biosciences and Engineering, 2018, 15(6): 1345-1385. doi: 10.3934/mbe.2018062

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  • In this paper, we derive a chemotaxis model with degenerate diffusion and density-dependent chemotactic sensitivity, and we provide a more realistic description of cell migration process for its early and late stages. Different from the existing studies focusing on the case of non-degenerate diffusion, this model with degenerate diffusion causes us some essential difficulty on the boundedness estimates and the propagation behavior of its compact support. In the presence of logistic damping, for the early stage before tumour cells spread to the whole domain, we first estimate the expanding speed of tumour region as O(tβ) for 0<β<12 . Then, for the late stage of cell migration, we further prove that the asymptotic profile of the original system is just its corresponding steady state. The global convergence of the original weak solution to the steady state with exponential rate O(ect) for some c>0 is also obtained.


    1. Introduction

    The motion of cells moving towards the higher concentration of a chemical signal is called chemotaxis. For example, bacteria moves toward the highest concentration of food molecules to find food. A well-known chemotaxis model was initially proposed by Keller and Segel [15] in 1971, subsequently, a number of variations of the Keller-Segel system were proposed and have been extensively studied during the past four decades, for example, see the survey papers [1,12] and the references therein. Especially, chemotaxis models also appear in medical mathematics. Many factors effect the migration mechanisms of tumour cells. For example, the extracellular matrix (ECM), to which the tumour cell to be attached, inhibits the cell polarizes and elongates to migrate. ECM-degrading enzymes (MDE) cleave ECM fibers into smaller chemotactic fragments to facilitate cell-migration [6]. In [4], Chaplain and Anderson introduced a model for tumour invasion mechanism, which describes tumour invasion phenomenon in accounting for the role of chemotactic ECM fragments named ECM*, produced by a biological reaction between ECM and MDE. In these models, the tumour cell random motility is assumed to be a constant, which leads to linear isotropic diffusion. However, in realistic situation, it is emphasized that migration of the tumour cells through the ECM fibers should rather be regarded like movement in a porous medium with degenerate diffusion from a physical point of view [38]. Compared with the classical tumour invasion model with linear diffusion, the mathematical analysis of the nonlinear diffusion system has to cope with considerable additional challenges and is much less understood. Several chemotaxis models with nonlinear diffusion have been recently proposed and analyzed, e.g. [18,38,45,46], where the nonlinear diffusions in these studies were still assumed to be non-degenerate. For tumour angiogenesis model and relevant mathematical analysis with or without degenerate diffusion, we refer to [14,22,23,48,49,50,52,54] and the references therein.

    Tumour cells can modify their migration mechanisms in response to different conditions [6]. There are two potentially important factors: (ⅰ) the effect of cell-density on the probability of cell movement; (ⅱ) the effect of signal-mediated cell-density sensing mechanisms on movement [28]. For interacting cell population, Painter and Sherratt [29] further presented four different sensing strategies: strictly local, neighbour based, local average and gradient. Cell movement involves the processing of multiple signals, each of them may act on the cells in different ways. For neighbor-based and gradient-based rules, Painter and Hillen [28] proposed volume filling approach, that is, the movement of cells is inhibited by the neighboring site where the cells are densely packed. Inspired by the idea of Painter et al. [28,29] and recently in Xu et al. [57], we extend Chaplain and Anderson's model [4] to a new one with density-dependent jump probability of tumour cells as follows, which is concerned with the competition between the following several biological mechanisms: degenerate diffusion, density-dependent chemotaxis, and general logistic growth. That is,

    {ut=(q(u)u)(q(u)uv)+μuδ(1ru),xΩ,t>0,vt=Δv+wz,xΩ,t>0,wt=wz,xΩ,t>0,zt=Δzz+u,xΩ,t>0. (1)

    The detailed derivation of the model (1) will be carried out in the Appendix. Here, Ω is a bounded domain in Rn with smooth boundary. The four variables u, w, z and v represent the cancer cell density, ECM concentration, the MDE concentration and the ECM* concentration, respectively. q(u) denotes the jump probability of a cell depending on the population pressure at its present location, which is increasing with respect to u with q(0)=0, q(1)=1, namely, the jump probability is 1 when the cell density exceeds maximum and it is zero when the cell density is zero, and f(u)=μuδ(1ru) is the logistic growth term, where μ>0 and r>0 are the proliferation rate and reciprocal of carrying capacity, δ1 is a constant.

    The unbiased cell movement modelled by linear diffusion motility mechanism has been used extensively to study a variety of cell biology problems. However, when cells are close enough for regular contacts, they will inevitably interact [29]. Linear diffusion of each cell type is inappropriate for the close-packed cell populations involved in early tumour growth. The degenerate nonlinear diffusion can represent ''population pressure'' in cell invasion models [29], which arises from the ecology dispersal literature [9,10,24,58]. A high cell density results in increased probability of a cell being ''pushed'' from a site. In this case, large dispersal takes place in highly populated regions, but low mobility occurs in the regions of low cell density. The cell invasions described by nonlinear degenerate systems with the density-dependent nonlinear diffusivity function q(u)=Dum1 with m>1 in the diffusion term (q(u)u) have been paid more attention in recent years [13,39,53,57]. These tumour invasions models with porous media diffusion is degenerate at u=0, that is, when the population density is zero, the diffusion coefficient is zero. In fact, biological evidence suggests that no cell migration (in particular no diffusivity) occurs in noncellular regions [20,59].

    Some studies found that degenerate nonlinear diffusion model related to the porous media equation (PME) provides a better match to experimental cell density profiles [34]. Sengers and coworkers [30] developed a set of in vitro cell invasion experiments and image analysis to quantify the migration and proliferation of two different skeletal cell types, including human osteosarcoma MG63 cells and human bone marrow stromal cells (HBMSCs). Comparison of experimental and simulated cell distribution are shown in Fig. 1 in [30], where the cell density considerably increased and simultaneously spread outwards from the centre of the cell circle, producing a new cell migration front every day. Their results show that the MG63 migration with sharp front is best described by a degenerate diffusion model with the diffusivity q(u)=um1 with m=2 [Fig. 1(a)], while the HBMSC migration with smooth front corresponds to the solution of a linear diffusion equation [Fig. 1(b)]. Similarly, Sherratt and Murray's work provides a physical connection between epidermal wound healing experimental data and the solutions of either the linear diffusion equation or the porous media equation to represent cell density profiles [33]. They showed that the solution of degenerate diffusion model with the diffusivity function q(u)=u3 compare well with the experimental data in [42]. Mathematically, the PME raises the possibility of sharp-front waves, whereas the smooth-front waves arise in linear diffusion equations. The difference between these front types is that the sharp-front waves have distinct boundaries, and the population density decreases to zero at a finite point in space, rather than tending to zero asymptotically [31,43,55].

    Figure 1. (a) Comparison of experimental and simulated cell distribution for MG63 cells. The measured cell density (gray histogram) are fitted using the solution of degenerate nonlinear diffusion model (gray lines). (b) Comparison of experimental and simulated cell distribution for HBMSC cells. The measured cell density (gray histogram) are matched with the solution of linear diffusion model (gray lines). This diagram was redrawn from the one in Ref. [30].

    An interesting work related to the chemotaxis model mentioned above is [7], in which they considered the following chemotaxis system with linear diffusion

    {ut=Δu(uv),xΩ,t>0,vt=Δv+wz,xΩ,t>0,wt=wz,xΩ,t>0,zt=Δzz+u,xΩ,t>0. (2)

    It is proved the existence of global solutions and the asymptotic behaviors of global solutions as time goes to infinity by using the properties of the Neumann heat semigroup etΔ in Ω. Recently, Li et al. [17] study the the quasilinear chemotaxis system (2) with the effect of the nonlinear diffusion q(u)Cum1 with C>0 and the nonlinear chemotactic sensitivity function S(x,u,v) with some structural conditions for the above coupled tumor invasion system. They obtained the boundedness and large time behavior for this system.

    Apart from the diffusive motility, another important mechanism in cell invasion is cell proliferation. In [35], an assay using gut organ culture validates that proliferation at the invading front is the critical mechanism driving apparently directed invasion. Cells at the invasive front are proliferative and migrate into previously unoccupied tissue. It also has important implications for carcinoma invasion. Tumour invasion systems with proliferative cells have been studied extensively [8,21,26]. Logistic growth is one of important models of proliferation to a carrying capacity limit [24]. Von Bertalanffy derived a general logistic growth law for avascular tumour growth [44], and suggested that

    f(u)=γuλδuμ,

    where γ,λ,δ,μ>0 and μ>λ. In our tumour invasion model, the cell proliferation also plays an important role in biological modelling and theoretical study for the evolution of tumour boundary. Based on the structure of degenerate diffusion equation with the Von Bertalanffy's growth law, we compare its solution with the weak upper and lower Barenblatt-type self-similar solutions and we obtain the upper and lower bounds of the expanding rate of its support. These results provide mathematical predictions of the evolution of the tumour invasion boundary. In the proof of the lower bound of the expanding rate of its support, we utilize the combination of the degenerate diffusion and the proliferation from the logistic growth to balance the possible aggregation effect due to the chemotaxis, since this chemotaxis may cause backward diffusion and negative effects on the expanding of the support. Without this logistic growth, we find that the degenerate diffusion alone is insufficient to govern the possible aggregation effect. We note that the upper bound of the expanding rate of the support (i.e. the finite speed propagation property) is also valid for the system without logistic growth, whereas the lower bound of the support or the expanding property is insufficient in this case.

    Compared to the linear cases, the chemotactic system with degenerate diffusion and chemotactic sensitivity is more complex and challenging. Since the first equation of (1) is degenerate at any point where u(x,t)=0, there is no classical solution in general. The spatial derivatives of u may not exist in classical sense, and may even do not belong to the class of locally integrable generalized functions, that is, there might hold uW2,1loc.

    In this paper, we provide a more realistic description of cell migration process for early and late stages. It is worth to mention that our stability results of the model (1) give a certain estimate for the speed of the expanding speed of tumour region. We construct suitable subsolutions and supersolutions to show the position of the free boundary for the tumour region. Then, we prove that there exist t0 and two families of monotone increasing open sets {A1(t)}t>0, {A2(t)}t(0,t0) such that

    A1(t)suppu(,t)¯A2(t)Ω,t(0,t0),

    A1(t) and A2(t) have finite derivatives with respect to t, namely, {A1(t)}t>0 and {A2(t)}t(0,t0) both expand at finite speeds. This indicates the finite speed propagation property of our chemotaxis model. As shown late in Remarks 1 and 2, in the porous media diffusion case, we estimate that, at the early stage the expanding speed of tumour region is somehow like the algebraic rate of (1+t)β for some β(0,12). This resembles the case of the Stefan problem with a linear diffusion term.

    As we all know, for linear diffusion equations with initial data u0, the solution u(x,t)>0 for t>0 and any xRN, thus a linear diffusion process predicts a non-zero u for arbitrarily large displacements at arbitrarily small time, namely, the underlying propagation speed is infinite [43]. This means that the initial tumour cells moving into regions of unoccupied tissue immediately in this biological system. However, the spatial support of the solution to the degenerate diffusion equation remains bounded for all time t>0 [5]. There are distinct boundaries, called interfaces, beyond which the population density is zero. Our stability results of the tumour model with degenerate nonlinear diffusion provide a possible method to study the evolution of cell migration boundary theoretically.

    An in vivo primary tumour initially develops in epithelia and grows within the epithelium before expanding into surrounding tissues [32]. The very early stages of tumour growth are rarely seen clinically due to the small size of the cell masses. However, this early growth has been well studied in vitro using HEPA-1 tumour cells. Small aggregates of several cells formed during the initial hours in culture and accounted for the rapid increase in the mean volume of the cell spheroids. This assay was introduced by Leek [16] in 1999. Then, Owen et al. compared their numerical simulations with this experimental data. There is a good agreement between the experimental and numerical results for the outer spheroid radius [27]. Key results from their study are shown in Fig. 2. Growth was rapid for the initial days, decreased, and approached a horizontal asymptote. It can be difficult to decide what type of model is best suited to a particular biological problem. Different approaches in mathematics can reproduce the same experimental results [3]. Our theoretical results also provide a good fit to the experimental results in [16]. The shape of the growth curve of the cell spheroids is similar to the graph of power function R(t)=(1+t)γ with 0<γ<1. Note that, our estimation of the expanding speed of tumour region with the algebraic rate of (1+t)β for some β(0,12) compares well with this experimental data. It indicates that the tumour cell model described by the degenerate nonlinear diffusion motility mechanism can describe the progress of the very early stage of tumor growth mathematically. In combination with experiments, this type of tumour model may prove useful in predicting the evolution of tumour cell migration, investigating subsequent stages of tumour progression and testing therapeutic strategies.

    Figure 2. The growth curve of HEPA-1 spheroids. The solid line represents the position of the outer tumour boundary. Dimensional diameters are shown in μm. This diagram was redrawn from the one in Ref. [27].

    In contrast with the well known linear cases, the degenerate diffusion is endowed with the interesting feature of slow diffusion, that is, the compact support of solutions propagates at a finite speed. The slow diffusion feature has some advantages and accuracy for describing specified biological processes in the point of view of the physical reality, and it also leads to more challenges in the mathematical studies. For example, in order to investigate the asymptotic behavior of solutions, one must appropriately describe the propagation behavior of its support, which is more likely to be a compact subset of the prescribed domain for some time interval if the initial data are given so. We mention that the Neumann heat semigroup theory and functional transform methods have been proved to be effective in studying the global boundedness and large time behavior for the linear diffusion equations, but they are all inapplicable in the degenerate diffusion case due to the nonlinearity. We establish the global existence of bounded weak solutions to this model by energy estimate technique and methods based on Moser-type iteration. Then we prove that, at the late stage of the tumour migration, the original weak solution time-asymptotically converges to its steady state, even if the initial perturbation is large, namely, the global stability of the steady state. The adopted approach is the technical compactness analysis with the help of the comparison principle deduced by the approximate Hohmgren's approach and two kinds of lower solutions showing the expanding support and the exponentially convergence. The one is a self similar weak lower solution of Barenblatt type and the other kind is an ODE solution.

    This paper is organized as follows. In Section 2, we state our main results. We leave the global existence of weak solutions to the corresponding chemotaxis system and their regularity into Section 3 as preliminaries. Section 4 is devoted to the study of compact support property of the tumour cells at early stage and the large time behavior at late stage, showing the exponentially convergence of solutions.


    2. Main results

    In this section, we first state our main results on the study of expanding compact support of the tumour cells at early stage and the asymptotic behavior at late stage. We leave the detailed derivation on the new chemotaxis model (1) with density-dependent jump probability in the Appendix. We estimate the upper bound and lower bound for expanding speed of tumour cell region at early stage (before the tumour cells spread to the whole body) and show the exponentially convergence of solutions for large time.

    We consider the following system (3) with degenerate diffusion

    {ut=Δ(q(u)u)(q(u)uv)+μuδ(1u),vt=Δv+wz,wt=wz,zt=Δzz+u,xΩ,t>0,uν=vν=zν=0,xΩ,t>0,u(x,0)=u0(x),v(x,0)=v0(x),w(x,0)=w0(x),z(x,0)=z0(x),xΩ, (3)

    where δ1, μ>0, u0,v0,w0,z0 are nonnegative functions, ν is the unit outer normal vector, and q(u)0 with q(0)=0. Here and after, the IBVP (3) will be our main target equations.

    Since degenerate diffusion equations may not have classical solutions in general, we need to formulate the following definition of generalized solutions for the initial boundary value problem (3).

    Definition 2.1. Let T(0,). A quadruple (u,v,w,z) is said to be a weak solution to the problem (3) in QT=Ω×(0,T) if

    (1) uL(QT), (q(u)u)L2((0,T);L2(Ω)), and q(u)utL2((0,T);L2(Ω));

    (2) vL(QT)L2((0,T);W2,2(Ω))W1,2((0,T);L2(Ω));

    (3) wL(QT), wtL2((0,T);L2(Ω));

    (4) zL(QT)L2((0,T);W1,2(Ω))W1,2((0,T);L2(Ω));

    (5) the identities

    T0Ωuψtdxdt+Ωu0(x)ψ(x,0)dx=T0Ω(q(u)u)ψdxdtT0Ωq(u)uvψdxdtT0Ωμuδ(1u)ψdxdt,T0Ωvtφdxdt+T0Ωvφdxdt=T0Ωwzφdxdt,T0Ωwtφdxdt=T0Ωwzφdxdt,T0Ωztφdxdt+T0Ωzφdxdt=T0Ω(uz)φdxdt,

    hold for all ψ,φL2((0,T);W1,2(Ω))W1,2((0,T);L2(Ω)) with ψ(x,T)=0 for xΩ;

    (6) (v,w,z) takes the value (v0,w0,z0) in the sense of trace at t=0.

    If (u,v,w,z) is a weak solution of (3) in QT for any T(0,), then we call it a global weak solution.

    A quadruple (u,v,w,z) is said to be a globally bounded weak solution to the problem (3) if there exists a constant C such that

    suptR+{uL(Ω)+vW1,(Ω)+wL(Ω)+zW1,(Ω)}C.

    Throughout this paper we assume that q(u)=um1 with m>1, and the initial data satisfy u0C(¯Ω), v0W2,(Ω), w0C2,θ(¯Ω), θ(0,1), w0ν=0 on Ω, z0C(¯Ω). Here we note that for constant initial data (u0,v0,w0,z0), the first equation of (3) is reduced to

    u(t)=μuδ(1u),u(0)=u0,

    which is ill-posed if 0<δ<1. Therefore, we only consider the case δ1.

    As preliminaries, we leave the global existence and regularity results into Section 3. Our main results concerned with the description of cell invasion processes are as follows. First, we show that the evolution of tumour invasion in the very early stage.

    Theorem 2.2 (Early stage profile - upper bound). Let (u,v,w,z) be a globally bounded weak solution of (3) with the initial data

    suppu0¯Br0(x0)Ω,

    for some r0>0 and x0Ω. Then there exists a time t1>0 and a family of monotone increasing open sets {A(t)}t(0,t1) such that

    suppu(,t)¯A(t)Ω,t(0,t1),

    and A(t) has a finite derivative with respect to t. More precisely, we can choose

    A(t)={xΩ;|xx0|2<η(τ+t)},t(0,t1),

    with some appropriate η,τ>0.

    Remark 1. As a typical finite propagating model, the Barenblatt solution of the porous medium equation is

    B(x,t)=(1+t)k[(1k(m1)2mn|x|2(1+t)2k/n)+]1m1 (4)

    with k=1/(m1+2/n)<n/2 for m>1, and its support is expanding at the rate (1+t)k/n. Here we have proved the tumour cells are located within a ball expanding at the rate (1+t)1/2. We note that the upper bound of the expanding rate of the support is also valid for the system without logistic growth.

    Next, we show the propagating property of the tumour cells at the early stage.

    Theorem 2.3 (Early stage profile - lower bound). Let (u,v,w,z) be a globally bounded weak solution of (3). Assume that 1δ<m, Ω is convex and u00. Then there exists a time t2>0 such that the support of u expands to the whole Ω when tt2. Precisely speaking, there exist a family of monotone increasing open sets {A(t)}t>0 (we can choose A(t)={xΩ;|xx0|2<η(1+t)β} with sufficiently small β,η>0) such that

    A(t)suppu(,t),t>0,

    and A(t)=Ω for tt2, A(t) has a finite derivative with respect to t.

    Remark 2. For this chemotaxis system, we proved that the tumour cells will expand to the whole body when the time t increases. Compared with the porous medium equation, whose Barenblatt solution B(x,t) in (4) is expanding at the rate (1+t)2k/n, the tumour cells of (3) migrate to at least a ball expanding at the rate (1+t)β. Here in the proof we have selected β>0 sufficiently small, which means the support is expanding with a much slower rate.

    Under the hypotheses of Theorem 2.2 and Theorem 2.3, we see that there exist t0 and two family of monotone increasing open sets {A1(t)}t>0, {A2(t)}t(0,t0) such that

    A1(t)suppu(,t)¯A2(t)Ω,t(0,t0),

    A1(t) and A2(t) have finite derivatives with respect to t, which means that {A1(t)}t>0 and {A2(t)}t(0,t0) both expand at finite speeds. This indicates immediately the finite speed propagation property of this chemotaxis model.

    After the tumour cells spread to the whole domain, we can investigate the large time behavior. We show that the solution converges to its steady state exponentially.

    Theorem 2.4 (Late stage profile). Let (u,v,w,z) be a globally bounded weak solution of (3). Assume that the hypothesis in Theorem 2.3 is valid. Then there exist C and c>0 such that

    u(,t)1L(Ω)+w(,t)W1,(Ω)+v(,t)(¯v0+¯w0)W2,(Ω)+z(,t)1L(Ω)Cect,

    for all t>0, where ¯v0=1|Ω|Ωv0(x)dx and ¯w0=1|Ω|Ωw0(x)dx.

    The main difficulty lies in proving the expanding property of the support of the first component u. We first prove the comparison principle by the approximate Hohmgren's approach, and then construct two kinds of lower solutions. The one is a self similar weak lower solution with much slower expanding support and slightly faster decaying maximum compared with the Barenblatt solution to the porous medium equation, the other kind is an ODE solution. After showing the expanding property, we formulate several upper and lower solutions that converge to steady state exponentially by utilizing the exponential decay of other components.


    3. Preliminaries: Global existence, boundedness and regularity

    As preliminaries, we prove the existence, boundedness and regularity of a global weak solution in this section. The main preliminary results are as follows.

    Theorem 3.1 (Existence of globally bounded weak solutions). For 1n3, the problem (3) admits a globally bounded weak solution (u,v,w,z).

    Theorem 3.2 (Regularity). Let (u,v,w,z) be a globally bounded weak solution of (3). Then there exist α(0,1) and C(p)>0 such that

    uL(Ω×(t,t+1))+vC2+α,1+α/2(¯Ω×[t,t+1])+wCα(¯Ω×[t,t+1])+zW2,1p(Ω×(t,t+1))C(p),

    for any p>1 and t1.

    We first use the artificial viscosity method to get smooth approximate solutions. Despite the absence of comparison principle, we can prove a special case compared with a lower solution, which is helpful for establishing the regularity estimates. By making use of the special structure of dispersion, we carry on the estimates on um in W1,2(QT), instead of u. These energy estimates ensure the global existence of weak solution.

    Consider the following corresponding regularized problem

    {ut=(m(aε(u))m1u)(umv)+μ|u|δ1u(1u)+ε,vt=Δv+wz,wt=wz,zt=Δzz+u,xΩ,t>0,uν=vν=zν=0,xΩ,t>0,u(x,0)=u0ε(x),v(x,0)=v0ε(x),w(x,0)=w0ε(x),z(x,0)=z0ε(x),xΩ, (5)

    where ε(0,1), aεC(R), aε(s)=s+ε for s0, aε(s)=ε/2 for s<ε, aε is monotone increasing with 0aε1, and u0ε,v0ε,w0ε,z0ε are smooth approximations of u0,v0,w0,z0, respectively, with

    εu0εu0+ε,0v0εv0+ε,0w0εw0+ε,0z0εz0+ε,|u0ε|2|u0|,|v0ε|2|v0|,|w0ε|2|w0|,|Δw0ε|2|Δw0|,|z0ε|2|z0|,

    and w0εν=0 on Ω. The local existence of the regularized problem (5) is trivial and we denote the unique solution by (uε,vε,wε,zε). Let (0,Tmax) be its maximal existence interval.

    As usual, there is no comparison principle for the system, because the system is strongly coupled. However, we have the following lemma.

    Lemma 3.3. There holds uε0, vε0, wε0, and zε0 for all xΩ and t(0,Tmax).

    Proof. We denote (uε,vε,wε,zε) by (u,v,w,z) in this proof for the sake of simplicity. We argue by contradictions. Since u0εε>0, there exists t0(0,Tmax) such that u>0 for all xΩ and t(0,t0), u(x0,t0)=0 for some x0¯Ω and u(x,t0)0 for all xΩ.

    Now we divide this proof into two parts. If x0Ω, then u(x0,t0)=0 and

    (m(aε(u))m1u)=m(aε(u))m1Δu+m(m1)aε(u)|u|20,(umv)=umΔv+mum1uv=0,μ|u|δ1u(1uw)=0,

    which contradicts to ut(x0,t0)0.

    If x0Ω, then uτ(x0,t0)=0, 2uτ2(x0,t0)0 for any tangent vector τ, and the boundary condition shows that uν(x0,t0)=0. We assert that 2uν2(x0,t0)0. In fact, if it were not true, Taylor expansion at (x0,t0) shows that there would exist a point xΩ such that u(x,t0)<0. Therefore, we also have u(x0,t0)=0 and the above equalities. Those contradictions complete the proof.

    Since uε0, the first equation of (5) is equivalent to

    ut=Δ(u+ε)m(umv)+μuδ(1u)+ε,u0.

    Now we present some energy estimates independent of time t and the parameter ε.

    Lemma 3.4. The first solution component uε satisfies

    supt(0,Tmax)Ωuε(,t)dxmax{Ωu0dx+|Ω|,(2(C1+|Ω|)μC2)1/(δ+1)},

    where C1=μ2δ|Ω| and C2=1/|Ω|δ.

    Proof. We denote uε by u in this proof for the sake of simplicity. Since u is nonnegative and uν=vν=0 on Ω, integration of the first equation of (5) over Ω yields

    ddtΩudxμΩuδdxμΩuδ+1dx+|Ω|,

    for all t(0,Tmax). We note that

    μΩuδdx12μΩuδ+1dx+C1,

    and

    Ωuδ+1dxC2(Ωudx)δ+1,

    where C1=μ2δ|Ω| and C2=1/|Ω|δ. Let y(t)=Ωu(,t)dx for t[0,Tmax). We find

    y(t)C1+|Ω|μC22yδ+1(t).

    The comparison principle of ODE shows that

    y(t)max{y(0),(2(C1+|Ω|)μC2)1/δ+1}

    for all t(0,Tmax).

    Here we recall some lemmas about the Lp-Lq type estimates for the components of the solution, and we refer the readers to [7] for details.

    Lemma 3.5 ([7]). Let p1 and

    {q[1,npn2p),pn2,q[1,],p>n2.

    Then for any T(0,Tmax], there exists a constant Cz(p,q) such that

    supt(0,T)zε(,t)Lq(Ω)Cz(p,q)(z0Lq(Ω)+supt(0,T)uε(,t)Lp(Ω)).

    Lemma 3.6 ([7]). Let q1 and

    {r[1,nqnq),qn,r[1,],q>n.

    Then for any T(0,Tmax], there exists a constant Cv(q,r) such that

    supt(0,T)vε(,t)Lr(Ω)Cv(q,r)(v0Lr(Ω)+supt(0,T)zε(,t)Lq(Ω)).

    Lemma 3.7. There holds

    wε(,t)L(Ω)w0L(Ω)+1,t(0,Tmax),

    and

    Ωvε(x,t)dxΩv0(x)dx+Ωw0(x)dx+2|Ω|,t(0,Tmax).

    Proof. Since both wε and zε are nonnegative, it is clear from the third equation of (5) that

    |wε(x,t)|w0ε(x,t)w0L(Ω)+1.

    We add the third to the second equation of (5) and integrate over Ω to obtain

    ddtΩ(vε+wε)dx=ΩΔvεdx=0,t(0,Tmax).

    Thus,

    Ω(vε+wε)dxΩv0ε(x)dx+Ωw0ε(x)dxΩv0(x)dx+Ωw0(x)dx+2|Ω|,

    for all t(0,Tmax).

    Lemma 3.8. Let 1n3. There exists a constant C independent of t and ε such that

    vεL(Ω)C,t(0,Tmax).

    For any r1, there exists a constant C(r) independent of t and ε such that

    vεLr(Ω)C(r),t(0,Tmax).

    Proof. According to Lemma 3.4, uεL1(Ω) is uniformly bounded. Since n3, we can apply Lemma 3.5 and 3.6 to complete this proof.

    The following Gagliardo-Nirenberg inequality (see [46,51]) will be used in deriving the Lp estimates of uε.

    Lemma 3.9. Let 0<sp2n(n2)+. There exists a positive constant C such that for all uW1,2(Ω)Ls(Ω),

    uLp(Ω)C(uaL2(Ω)u1aLs(Ω)+uLs(Ω))

    is valid with a=n/sn/p1n/2+n/s(0,1).

    We present the following Lp estimate of uε.

    Lemma 3.10. Let 1n3. For any given p1, there exists a constant C(p)>0 independent of t and ε such that

    uε(,t)Lp(Ω)C(p),t(0,Tmax).

    Proof. We denote uε,vε by u,v in this proof for the sake of simplicity. By a straightforward computation, testing the first equation in (5) by ur for r>0 and integrating by parts we find that

    1r+1ddtΩur+1dx+Ω(u+ε)murdxΩumvurdx+μΩuδ+rdxμΩuδ+r+1dx+Ωurdx. (6)

    We note that

    μΩuδ+rdx14μΩuδ+r+1dx+C1, (7)

    and

    Ωurdx14μΩuδ+r+1dx+C2, (8)

    where C1 and C2 are constants independent of t. Then by Young's inequality, we see that

    ΩumvurdxrΩum+r1|vu|dxmr2Ω(u+ε)m1ur1|u|2dx+r2mΩum+r|v|2dx12Ω(u+ε)murdx+r2mΩum+r|v|2dx. (9)

    We use Hölder's inequality to see that

    r2mΩum+r|v|2dxr2m(Ωum+r+κdx)m+rm+r+κ(Ω|v|2(m+r+κ)κdx)κm+r+κC3(Ωum+r+κdx)m+rm+r+κ

    where κ>0 is a constant to be determined and C3 is a constant depending on the L2(m+r+κ)κ(Ω) norm of v which is uniformly bounded according to Lemma 3.8. Now we use the Gagliardo-Nirenberg inequality Lemma 3.9 to obtain

    (Ωum+r+κdx)m+rm+r+κ=um+r22L2(m+r+κ)m+r(Ω)C4(um+r22aL2(Ω)um+r22(1a)L2m+r(Ω)+um+r22L2m+r(Ω))C5(1+um+r22aL2(Ω)),

    where C4 is a constant, C5 depends on uL1(Ω), and

    a=n(m+r)/2n(m+r)/(2(m+r+κ))1n/2+n(m+r)/2(0,1),

    provided that 2(m+r+κ)m+r<2n(n2)+. This can be done by taking κ>0 and appropriately small. Therefore, we have

    r2mΩum+r|v|2dxC3C5(1+um+r22aL2(Ω))2mr(m+r)2um+r22L2(Ω)+C6mr2Ω(u+ε)m1ur1|u|2dx+C612Ω(u+ε)murdx+C6, (10)

    since a(0,1). Combining (7), (8), (9), (10) with (6), we infer that

    ddtΩur+1dxμ(r+1)2Ωuδ+r+1dx+(r+1)(C1+C2+C6).

    According to

    Ωuδ+r+1dx1|Ω|δr+1(Ωur+1dx)δ+r+1r+1,

    we obtain

    ddtΩur+1dx(r+1)(C1+C2+C6)μ(r+1)2|Ω|δr+1(Ωur+1dx)δ+r+1r+1.

    By an ODE comparison,

    Ωur+1dxmax{Ω(u0+1)r+1dx,(2(C1+C2+C6)|Ω|δr+1μ)r+1δ+r+1}

    for all t(0,T).

    Lemma 3.11. Let 1n3. There exists a constant C>0 independent of Tmax and ε such that

    supt(0,Tmax)vεL(Ω)C.

    Proof. According to Lemma 3.10, uεLn+1(Ω) is uniformly bounded. We can apply Lemma 3.5 and Lemma 3.6 to obtain the boundedness of vεL(Ω).

    We now employ the following Moser-type iteration to get the L(Ω) estimate of u.

    Lemma 3.12. Let 1n3. There exists a constant C>0 independent of Tmax and ε such that

    supt(0,Tmax)uεL(Ω)C.

    Proof. We denote uε,vε by u,v in this proof for the sake of simplicity. We test the first equation in (5) by ur for r>0 and integrating by parts we find that

    1r+1ddtΩur+1dx+Ω(u+ε)murdxΩumvurdx+μΩuδ+rdxμΩuδ+r+1dx+Ωurdx. (11)

    Similar to the proof of Lemma 3.10, using Young's inequality we can estimate

    μΩuδ+rdx14μΩuδ+r+1dx+4δ+rμ|Ω|,Ωurdx14μΩuδ+r+1dx+(4μ)rδ+r|Ω|,

    and

    ΩumvurdxrΩum+r1|vu|dxmr4Ω(u+ε)m1ur1|u|2dx+rmΩum+r|v|2dx14Ω(u+ε)murdx+rmv2L(Ω)Ωum+rdx, (12)

    where according to Lemma 3.11 vL(Ω) is uniformly bounded. Now we apply the Gagliardo-Nirenberg inequality Lemma 3.9 to obtain

    Ωum+rdx=um+r22L2(Ω)C0(um+r22aL2(Ω)um+r22(1a)L1(Ω)+um+r22L1(Ω)),

    where a=n/(n+2)(0,1) and C0 is the constant in the Gagliardo-Nirenberg inequality which is independent of r. Therefore, we have

    rmv2L(Ω)Ωum+rdxrmv2L(Ω)C0(um+r22aL2(Ω)um+r22(1a)L1(Ω)+um+r22L1(Ω))mr(m+r)2um+r22L2(Ω)+(rmv2L(Ω)C0)11a((m+r)2mr)a1aum+r22L1(Ω)+rmv2L(Ω)C0um+r22L1(Ω)14Ω(u+ε)murdx+C1(r)um+r22L1(Ω), (13)

    where

    C1(r)=(rmv2L(Ω)C0)11a((m+r)2mr)a1a+rmv2L(Ω)C0.

    Inserting the above estimates (12), (13) into (11) yields

    ddtΩur+1dx+Ωur+1dxC1(r)(r+1)um+r22L1(Ω)+(r+1)(4δ+rμ|Ω|+(4μ)rδ+r|Ω|)+Ωur+1dx12μΩuδ+r+1dxC1(r)(r+1)um+r22L1(Ω)+C2(r), (14)

    where

    C2(r)=(r+1)(4δ+rμ|Ω|+(4μ)rδ+r|Ω|)+(2μ)r+1δ|Ω|.

    Now we use the following Moser-type iteration. Let r=rj, with rj=2j+m2 for jN+, that is, r1=m and

    rj1+1=rj+m2,jN+.

    We can invoke Lemma 3.10 to find C0 such that

    supt(0,Tmax)uLr1+1(Ω)C0.

    From (14) and an ODE comparison, we have

    supt(0,Tmax)urj+1Lrj+1(Ω)max{Ω(u0+1)rj+1dx,C1(rj)(rj+1)supt(0,Tmax)u2(rj1+1)Lrj1+1(Ω)+C2(rj)}. (15)

    A simple analysis shows that C1(r)(r+1)a1rb1 and C2(r)a2br2 for some positive constants a1,a2 and b1,b2 that all are greater than 1 and independent of r. Therefore, we can rewrite the above inequality (15) into

    supt(0,Tmax)urj+1Lrj+1(Ω)max{Ω(u0+1)rj+1dx,a1rb1jsupt(0,Tmax)u2(rj1+1)Lrj1+1(Ω)+a2brj2}. (16)

    Let

    Mj=max{supt(0,Tmax)Ωurj+1dx,1}.

    Since boundedness of u in L(Ω) is evident in the case when Mjmax{Ω(u0+1)rj+1dx,1} for infinitely many j1, we may assume that Mjmax{Ω(u0+1)rj+1dx,1} and thus, according to (16), there holds

    Mja1rb1jM2j1+a2brj2. (17)

    We note that if M2j1a2brj2 for infinitely many j1, then

    M1rj1+1j1(a2brj2)12(rj1+1)a1rj+m2brjrj+m22b2,

    for j sufficiently large, which shows the boundedness of u in L(Ω). Otherwise, M2j1a2brj2 except for a finite number of j1. Thus, there exists a j01 such that

    M2j1a2brj2,jj0.

    Therefore, we can rewrite (17) into

    Mj2a1rb1jM2j1DjM2j1 (18)

    for all jj0 with a constant D independent of j, whence upon enlarge D if necessary we can achieve that (18) actually holds for all j1. By introduction, this yields

    MjDj2i=0(ji)2jM2j11=D2j+2j1j2M2j11D2j+1M2j11

    for all j1, and hence that

    M1rj+1jD2j+12j+m1M2j12j+m10D2M1,

    for all j1. This implies that u indeed belongs to L(Ω×(0,Tmax)).

    Now we turn to the regularity estimates.

    Lemma 3.13. Let 1n3. Then there exists a constant C independent of t and ε such that

    supt(0,Tmax)(zεL(Ω)+zεL(Ω)+vεL(Ω)+vεL(Ω))C.

    And the third solution component wε fulfills

    wε(,t)L(Ω)2w0L(Ω)+(w0L(Ω)+1)supt(0,Tmax)zεL(Ω)t,

    for all t(0,Tmax).

    Proof. According to Lemma 3.12, Lemma 3.5, Lemma 3.6, we see that uεL(Ω, zεL(Ω, vεL(Ω are uniformly bounded in (0,Tmax). The standard LpLq type estimates also shows the boundedness of vεL(Ω and zεL(Ω. We denote vε,wε,zε by v,w,z in this proof for the sake of simplicity. Since both w and z are nonnegative according to the third and fourth equation in (5) and the initial data, we have

    w(x,t)=w0ε(x)et0z(x,τ)dτ,w(x,t)=w0ε(x)et0z(x,τ)dτw0ε(x)et0z(x,τ)dτt0z(x,τ)dτ.

    Therefore,

    |w(x,t)||w0ε(x,t)|+w0ε(x)supt(0,Tmax)zL(Ω)t2w0L(Ω)+(w0L(Ω)+1)supt(0,Tmax)zεL(Ω)t.

    This completes the proof.

    Lemma 3.14. There exists a constant C>0 independent of ε and T, such that

    T0Ω|Δvε|2dxdtC(1+T2),T(0,Tmax).

    Proof. We denote vε,wε,zε by v,w,z in this proof for the sake of simplicity. Multiplying the second equation in (5) by Δv and integrating over Ω yields

    Ωt|v|2dx+Ω|Δv|2dx=Ωv(wz)dxC(Ω|w|dx+1)C(1+t),

    since v, z and z are uniformly bounded in L(Ω) according to Lemma 3.13. Integrating over (0,T), we complete this proof.

    Lemma 3.15. There exists a constant C>0 independent of ε and T, such that

    T0Ω|umε|2dxdtC(1+T),T(0,Tmax).

    Proof. We denote uε,vε by u,v in this proof for the sake of simplicity. We test the first equation in (5) by (u+ε)m and get

    1m+1ddtΩ(u+ε)m+1dx+Ω|(u+ε)m|2dxΩumv(u+ε)mdx+μΩuδ(u+ε)mdxμΩuδ+1(u+ε)mdx+Ω(u+ε)mdx. (19)

    According to Lemma 3.11 and Lemma 3.12, v and u are uniformly bounded. Thus,

    Ωumv(u+ε)mdx12Ω|(u+ε)m|2dx+C1,

    where C1 is a constant independent of t and ε. Integrating (19) on (0,T) yields

    Ω(u+ε)m+1dx+T0Ω|(u+ε)m|2dxΩ(u0ε+ε)m+1dx+CT. (20)

    We note that

    |um|=mum1|u|m(u+ε)m1|(u+ε)|=|(u+ε)m|.

    This completes the proof.

    Lemma 3.16. There exists a constant C>0 independent of ε and T, such that

    T0Ω|(um+12ε)t|2dxdt+Ω|umε|2dxC(1+T2),T(0,Tmax).

    Moreover,

    T0Ω|(umε)t|2dxdt4m2(m+1)2uεm1L(Ω)T0Ω|(um+12ε)t|2dxdtC(1+T2),

    for all T(0,Tmax).

    Proof. We denote uε,vε by u,v in this proof for the sake of simplicity. We multiply the first equation in (5) by [(u+ε)m]t and then we have

    Ωm(u+ε)m1|ut|2dx+Ω(u+ε)m[(u+ε)m]tdxΩumv[(u+ε)m]tdx+μΩuδ[(u+ε)m]tdxμΩuδ+1[(u+ε)m]tds+Ω|[(u+ε)m]t|dx. (21)

    We note that uL(Ω) is uniformly bounded and then

    Ωμuδ[(u+ε)m]tdx=Ωmμuδ(u+ε)m1utdx15Ωm(u+ε)m1|ut|2dx+C1,Ωμuδ+1[(u+ε)m]tdx=Ωmμuδ+1(u+ε)m1utdx15Ωm(u+ε)m1|ut|2dx+C2,Ω|[(u+ε)m]t|dx=Ωm(u+ε)m1utdx15Ωm(u+ε)m1|ut|2dx+C3,

    where C1,C2,C3 are constants independent of t and ε. We also have

    Ωm(u+ε)m1|ut|2dx=4m(m+1)2Ω|((u+ε)m+12)t|2dx,

    and

    Ω(u+ε)m[(u+ε)m]tdx=12tΩ|(u+ε)m|2dx.

    There holds

    Ωumv[(u+ε)m]tdx=Ω[(u+ε)m]t(umv)dx=Ωm(u+ε)m1ut(mum1uv+umΔv)dx15Ωm(u+ε)m1|ut|2dx+C4Ω(u+ε)2(m1)|u|2dx+C5Ω|Δv|2dx15Ωm(u+ε)m1|ut|2dx+C4Ω|(u+ε)m|2dx+C5Ω|Δv|2dx,

    where C4 and C5 are constants independent of t and ε, since the uniform boundedness of vL(Ω). Inserting the above inequalities into (21), and noticing the inequality (20) in the proof of Lemma 3.15, we find a constant C independent of t and ε such that

    T0Ω|((u+ε)m+12)t|2dxdt+Ω|(u+ε)m|2dxΩ|(u0ε+ε)m|2dx+C(1+T2)C(1+T2).

    Clearly, we have

    |(um+12)t|2=(m+1)24um1|ut|2(m+1)24(u+ε)m1|ut|2=|((u+ε)m+12)t|2,

    and

    |(um)t|24m2(m+1)2uεm1L(Ω)|(um+12)t|24m2(m+1)2uεm1L(Ω)|((u+ε)m+12)t|2.

    The proof is completed.

    Proof of Theorem 3.1. According to the estimates, for any ε, the approximation solution (uε,vε,wε,zε) exists globally. The regularity estimates of vε,wε,zε are trivial. For any T(0,), we see that umεL(QT), umεL2(QT), and umε/tL2(QT), Thus, there exists a function ˜uW1,2(QT), such that umε weakly in W1,2(QT) and strongly in L2(QT) converges to ˜u. We denote u=˜u1/m since ˜u0. Thus, umε converges almost everywhere to um, and uε converges almost everywhere to u. We can verify the integral identities in the definition of weak solutions. By taking a sequence of T(0,) and the diagonal subsequence procedure, we can find the existence of a global weak solution.

    Now we show the regularity of the globally bounded weak solution.

    Lemma 3.17. Let (u,v,w,z) be a globally bounded weak solution of (3) such that u(,t)Lγ(Ω) is uniformly bounded with γ=max{1,n/3}. Then there exists a constant C such that

    suptR+{uL(Ω)+vW1,(Ω)+wL(Ω)+zW1,(Ω)}C.

    Proof. Since u(,t)Ln3(Ω) is uniformly bounded, for any r1 we can apply Lemma 3.5 and 3.6 to find a constant C(r) independent of t such that v(,t)Lr(Ω)C(r) for all t>0. The estimates in the proof of Theorem 3.1 in section 3 can be carried on to complete this proof here.

    In Lemma 3.13, we have proved w(,t)L(Ω)C(1+t) (same as wε) for some constant C>0. However that is an estimate depending on time t. Employing the method in the proof of Lemma 4.4 in next Section and iteration technique, we can prove the following uniform estimate.

    Lemma 3.18. Let (u,v,w,z) be a globally bounded weak solution of (3). Then for any p1 there holds

    Ω|w(,t)|pdxC(p),t>0,

    for some constant C(p) independent of time t.

    Proof. This proof proceeds along the idea of the arguments of Lemma 4.3 in [47] and Lemma 4.1 in [40]. Since

    w(x,t)=w0(x)et0z(x,s)ds,

    and

    w(x,t)=w0(x)et0z(x,s)dsw0(x)et0z(x,s)dst0z(x,s)ds.

    We see that

    |w(x,t)|22|w0(x)|2e2t0z(x,s)ds+2|w0(x)|2e2t0z(x,s)ds|t0z(x,s)ds|2.

    And thus

    Ω|w(x,t)|2dxC+CΩe2t0z(x,s)ds|t0z(x,s)ds|2dxCC2Ωe2t0z(x,s)ds(t0z(x,s)ds)dxC+C2Ωe2t0z(x,s)ds(t0Δz(x,s)ds)dxC+C2Ωe2t0z(x,s)ds(t0(zt+zu)ds)dxC+C2Ωe2t0z(x,s)ds(z(x,t)+t0z(x,s)ds)dxC.

    Using the same method, we have

    |w(x,t)|423|w0(x)|4e4t0z(x,s)ds+23|w0(x)|4e4t0z(x,s)ds|t0z(x,s)ds|4,

    and

    Ω|w(x,t)|4dxC+CΩe4t0z(x,s)ds|t0z(x,s)ds|4dxCC4Ωe4t0z(x,s)ds(t0z(x,s)ds)3dxC+3C4Ωe4t0z(x,s)ds(t0z(x,s)ds)2(t0Δz(x,s)ds)dxC+3C4Ωe4t0z(x,s)ds(t0z(x,s)ds)2(t0(zt+zu)ds)dxC+3C4Ωe4t0z(x,s)ds(t0z(x,s)ds)2(z(x,t)+t0z(x,s)ds)dxC+3C4Ωe2t0z(x,s)ds(t0z(x,s)ds)2dxsupxΩ[e2t0z(x,s)ds(z(x,t)+t0z(x,s)ds)]C,

    according to the proof of the previous estimate on wL2(Ω) and the boundedness of zL(Ω). Repeating this process for wLk(Ω) with k=6,8,, we complete this proof by iteration.

    Proof of Theorem 3.2. Lemma 3.18 shows the uniform bound of wLn+2(Ω). According to the third equation of (3), we see that wtL(Ω)=wzL(Ω)C. Therefore, wW1,n+2(Ω×(t,t+1)) and its norm is uniformly bounded for any t>0. Sobolev embedding theorem implies the existence of α(0,1) and C>0 such that

    wCα(¯Ω×[t,t+1])C,t>0.

    Since u is uniformly bounded, the strong solution theory of parabolic equation applied to the fourth equation in (3) shows

    ztLp(Ω×(t,t+1))+ΔzLp(Ω×(t,t+1))C(p),t>0,

    for some constant C(p)>0. Taking p>1+n/2, we see that for some α(0,1)

    zCα(¯Ω×[t,t+1])C,t>0.

    Thus,

    wzCα(¯Ω×[t,t+1])C,t>0.

    This can also be deduced by

    (wz)Lp(Ω)+(wz)tLp(Ω×(t,t+1))C,t>0,

    with p>n+1. Using bootstrap arguments involving the standard parabolic regularity theory, we can verify that

    vC2+α,1+α/2(¯Ω×[t,t+1])+zW2,1p(Ω×(t,t+1))C(p).

    The proof is completed.


    4. Propagating properties and large time behavier

    This section is devoted to the study of the propagating properties of the tumour cells and the large time behavior of the weak solution (u,v,w,z) to the problem (3). In contrast with the heat equation, it is known that the porous medium equation has the property of finite speed of propagation. Therefore, the first component u may not have positive minimum for some time t>0. We use the comparison principle together with two kinds of weak lower solutions, one is decaying but its support is expanding with finite speed of propagation, the other one is an increasing function of time t, to overcome the difficulty of degenerate dispersion.

    We first present the following comparison principle of the first component.

    Lemma 4.1. Let T>0 and the function space

    E={uL(QT);u0,umL2((0,T);L2(Ω)),um1utL2((0,T);L2(Ω))},

    u1,u2E, vL(QT), and u1, u2 satisfy the following differential inequalities

    {u1tΔum1(um1v)+μuδ1(1u1),u2tΔum2(um2v)+μuδ2(1u2),xΩ,t(0,T),u1ν0u2ν,xΩ,t(0,T),u1(x,0)u2(x,0)0,xΩ,

    in the sense that the following inequalities

    T0Ωu1φtdxdt+Ωu10(x)φ(x,0)dxT0Ωum1φdxdtT0Ωum1vφdxdtT0Ωμuδ1(1u1)φdxdt,T0Ωu2φtdxdt+Ωu20(x)φ(x,0)dxT0Ωum2φdxdtT0Ωum2vφdxdtT0Ωμuδ2(1u2)φdxdt,

    hold for some fixed u10,u20L2(Ω) such that u10u200 on Ω and all test functions 0φL2((0,T);W1,2(Ω))W1,2((0,T);L2(Ω)) with φ(x,T)=0 on Ω. Then u1(x,t)u2(x,t) almost everywhere in QT.

    Proof. The following inequality

    T0Ω(u1u2)φtdxdtT0Ω(um1um2)φdxdtT0Ω(um1um2)vφdxdtT0Ωμ(uδ1(1u1)uδ2(1u2))φdxdt,

    holds for all 0φL2((0,T);W1,2(Ω))W1,2((0,T);L2(Ω)) with φ(x,T)=0. Let

    a(x,t)={um1um2u1u2,u1(x,t)u2(x,t),mum11,u1(x,t)=u2(x,t),
    b(x,t)={(um1um2)vu1u2,u1(x,t)u2(x,t),mum11v,u1(x,t)=u2(x,t),

    and

    c(x,t)={μ(uδ1(1u1)uδ2(1u2))u1u2,u1(x,t)u2(x,t),μδuδ11μ(δ+1)uδ1,u1(x,t)=u2(x,t).

    Since v,u1,u2 are bounded, there exists a constant C>0 such that |b|Ca and |c|C. Henceforth, a generic positive constant (possibly changing from line to line) is denoted by C. However, c is not bounded by Ca and we have no estimate on c since we only assume that δ1. Then for all 0φL2((0,T);W1,2(Ω))W1,2((0,T);L2(Ω)) with φ(x,T)=0 on Ω and φν=0 on Ω×(0,T), there holds

    T0Ω(u1u2)(φt+a(x,t)Δφ+b(x,t)φ+c(x,t)φ)dxdt0.

    We employ the standard duality proof method or the approximate Hohmgren's approach to complete this proof (see Theorem 6.5 in [43], Chapter 1.3 and 3.2 in [56]). For any smooth function ψ(x,t)0, we solve the inverse-time problem

    {φt+(κ+aε(x,t))Δφ+b(x,t)φ+cθ(x,t)φ+ψ=0,(x,t)QT,φν=0,(x,t)Ω×(0,T),φ(x,T)=0,xΩ, (22)

    where κ>0, θ>0, aε is a smooth approximation of a, aεa, and

    cθ(x,t)={μ(uδ1(1u1)uδ2(1u2))u1u2,|u1(x,t)u2(x,t)|θ,0,|u1(x,t)u2(x,t)|<θ.

    This definition of cθ allows us to find a constant C(θ) such that

    c2θaC(θ).

    We may also need to replace b(x,t) and cθ(x,t) by their smooth approximation functions bε(x,t) and cθ,ε(x,t) respectively in (22). For the sake of simplicity we omit this procedure. Here we note that (22) is a standard parabolic problem as the initial data is imposed at the end time t=T. Therefore, it has a smooth solution φ0. Maximum principle shows the boundedness of φ. Then we get the estimate

    QT(u1u2)ψdxdtQT|u1u2||aaε||Δφ|dxdtκQT|u1u2||Δφ|dxdtQT|u1u2||ccθ|φdxdt=:I1I2I3.

    Now we need the a priori estimate on aε|Δφ|2. We can assume that T is appropriately small, otherwise we can prove step by step on each time interval. We multiply the equation (22) by η(t)Δφ where 1/2η(t)1 is a smooth function with η(t)M>0 for t(0,T). Since T is small, we can choose M appropriately large. Integrating over QT yields

    QTφtηΔφdxdt+QTη(κ+aε)(Δφ)2dxdtQTη|b||φ||Δφ|dxdt+QTηcθφΔφdxdt+QTηψΔφdxdtQTηCa|φ||Δφ|dxdt+14QTη(κ+aε)(Δφ)2dxdt+QTηc2θφ2κ+aεdxdt+QTη|ψ||φ|dxdt12QTη(κ+aε)(Δφ)2dxdt+QTηC2a2|φ|2κ+aεdxdt+QTηC(θ)φ2dxdt+QTη|ψ|2dxdt+QTη|φ|2dxdt.

    Using φ(x,T)=0, we have

    QTφtηΔφdxdt=QTηφφtdxdt=12QTηt|φ|2dxdt12QTη(t)|φ|2dxdtM2QT|φ|2dxdt.

    Therefore,

    QT|φ|2dxdt+QT(κ+aε)(Δφ)2dxdtC(θ). (23)

    It follows that

    I1=QT|u1u2||aaε||Δφ|dxdt(QT(κ+aε)|Δφ|2dxdt)12(QT|aaε|2κ+aε|u1u2|2dxdt)12C(θ)(QT|aaε|2κ+aεdxdt)12C(θ)κ12(QT|aaε|2dxdt)12,

    which converges to zero if we let ε0. For any fixed γ>0, denote

    Fγ={(x,t)QT;|u1u2|γ},

    and

    Gγ={(x,t)QT;|u1u2|<γ}.

    Then there exists a constant C(γ) such that a(x,t)C(γ) on Fγ and

    I2=κQT|u1u2||Δφ|dxdtκGγ|u1u2||Δφ|dxdt+κFγ|u1u2||Δφ|dxdtγGγκ|Δφ|dxdt+CκC(γ)12Fγa12|Δφ|dxdtCγ(QTκ|Δφ|2dxdt)12+CκC(γ)12(QTa|Δφ|2dxdt)12γC(θ)+κC(θ)C(γ)12,

    which converges to zero if we first let κ0 and then let γ0. We also have

    I3=QT|u1u2||ccθ|φdxdtC(QT|ccθ|2dxdt)12,

    which converges to zero if we let θ0. Now we conclude that

    QT(u1u2)ψdxdt0

    for any given ψ0 and then u1u2 almost everywhere on QT.

    Here we recall some lemmas about the asymptotic behavior of solutions to evolutionary equations.

    Lemma 4.2 ([7]). Let (u,v,w,z) be a global solution of (3). Then there exists a constant L0 such that

    v(,t)LW1,(Ω)0,ast.

    In particular,

    v(,t)L(Ω)0,ast.

    Lemma 4.3 ([47] Lemma 4.1). If z is a global classical solution of

    {zt=Δzz+u,xΩ,t>0,zν=0,xΩ,t>0,z(x,0)=z0(x),xΩ,

    where u(x,t)0 is given. Then there exist constants C1 and C2>0 only depend on diamΩ and supτ<tuL1(Ω) respectively, such that

    t0z(x,s)dsC1t0Ωu(y,s)dydsC2,xΩ,t>0.

    Lemma 4.4 ([47] Lemma 4.3, [40] Lemma 4.1). If (w,z) is a global solution of

    {wt=wz,zt=Δzz+u,xΩ,t>0,zν=0,xΩ,t>0,w(x,0)=w0(x),z(x,0)=z0(x),xΩ,

    with u0 on Ω×R+ and w0ν=0 on Ω, then

    Ω|w(,t)|2dx2Ω|w0|2dx+|Ω|2ew02L(Ω)+w02L(Ω)Ωz(,t)dx

    for all t>0.

    Now we construct a self similar weak lower solution with expanding support.

    Lemma 4.5. Let (u,v,w,z) be a globally bounded weak solution of (3) with the first component initial data u00, u00 and 1δ<m, Ω is convex. Define a function

    g(x,t)=ε(1+t)κ[(η|xx0|2(1+t)β)+]d,xΩ,t0,

    where d=1/(m1), β(0,1/2) is sufficiently small, κ=(1β)/(m1), x0Ω such that infxBr(x0)u0(x)>0 for some r>0, ε(0,1/2), η>0. Then by appropriately selecting β, ε and η, the function g(x,t) can be a weak lower solution of the first equation in (3), that is,

    {gtΔgm(gmv)+μgδ(1g),xΩ,t(0,T),gν0,xΩ,t(0,T),0g(x,0)u0(x),xΩ,

    in the sense that the following inequality

    T0Ωgφtdxdt+Ωg(x,0)φ(x,0)dxT0ΩgmφdxdtT0ΩgmvφdxdtT0Ωμgδ(1g)φdxdt,

    holds for any T>0 and all test functions such that 0φL2((0,T);W1,2(Ω))W1,2((0,T);L2(Ω)) with φ(x,T)=0 on Ω, and 0g(x,0)u0(x) on Ω. Therefore, u(x,t)g(x,t) and there exist t0>0 and ε00 such that u(x,t)ε0 for all xΩ and tt0.

    Proof. For simplicity, we let

    h(x,t)=(η|xx0|2(1+t)β)+,xΩ,t0,

    and

    A(t)={xΩ;|xx0|2(1+t)β<η},t0.

    Since u00, u00 and u0C(¯Ω), we see that there exists x0Ω such that u0(x)ε1 on Br(x0) for some r>0 and ε1>0. Without loss of generality, we may assume that Br(x0)Ω, x0=0 and ε11/2. Straightforward computation shows that

    gt=κε(1+t)κ1hd+ε(1+t)κdhd1β|x|2(1+t)β+1,gm=εm(1+t)mκmdhmd12x(1+t)β,Δgm=εm(1+t)mκmd(md1)hmd24|x|2(1+t)2βεm(1+t)mκmdhmd12n(1+t)β,

    for all xA(t) and t>0. According to the definition of g, we see that gν0 and gmν0 on Ω since Ω is convex, and

    g(x,0)=ε[(η|x|2)+]dε11Br(x0)u0(x),xΩ,

    provided that

    ηr2,εηdε1. (24)

    In order to find a weak lower solution g, we only need to check the following differential inequality on A(t)

    gtΔgm(gmv)+μgδ(1g),xA(t),t>0. (25)

    Since g(x,t)εηdε11/2, we see that μgδ(1g)μgδ/2 for all xΩ and t0. Further,

    |(gmv)|gm|Δv|+|mgm1||g||v|gmΔvL(Ω×R+)+(m+1)|gm|vL(Ω×R+).

    We denote C1=vL(Ω×R+) and C2=ΔvL(Ω×R+) for convenience, since they are bounded according to Theorem 3.2. A sufficient condition of inequality (25) is

    ε(1+t)κdhd1β|x|2(1+t)β+1+εm(1+t)mκmdhmd12n(1+t)β+C2εm(1+t)mκhmd+(m+1)C1εm(1+t)mκmdhmd12|x|(1+t)βκε(1+t)κ1hd+εm(1+t)mκmd(md1)hmd24|x|2(1+t)2β+μ2εδ(1+t)κδhdδ,xA(t),t>0. (26)

    As we have chosen d=1/(m1) and κ=(1β)/(m1), we rewrite (26) into

    εβm1|x|2(1+t)β+2nmm1εmh+C2εm(1+t)βh2+2(m+1)C1εmmm1h|x|κεh+εmm(m1)24|x|2(1+t)β+μ2εδ(1+t)κδ+κ+1hdδd+1,xA(t),t>0. (27)

    Let ε, β and η be chosen such that

    {εβ4εmmm1,2nmm1εm12κε,2mC1εm|x|12κε,C2εmhd+1dδμ2εδ(1+t)κδ+κ+1β,xA(t),t>0. (28)

    Since 1δ<m, β(0,1/2), κ=(1β)/(m1)1/[2(m1)], h1/2 and |x|diamΩ, we see that d+1dδ=d(mδ)>0, κδ+κ+1β=(mδ)κ>0. Thus, for (24) and (28), it suffices to choose η=r2,

    ε=min{(18nm)1m1,(18m(m1)C1diamΩ)1m1,ε1r2d,(μ2C2)1mδ},

    and then β=4εm1m/(m1).

    Now, we find a weak lower solution with expanding support and comparison principle Lemma 4.1 implies

    u(x,t)g(x,t)=ε(1+t)κ[(η|xx0|2(1+t)β)+]d,xΩ,t>0.

    There exists a t0 such that

    η|xx0|2(1+t0)βη2,xΩ,

    and thus

    u(x,t0)g(x,t0)ε(1+t0)κ(η2)d,xΩ.

    Next, we construct another constant lower solution

    u_(x,t)ε0,xΩ,t>t0,

    with 0<ε0ε(1+t0)κ(η/2)d1/2 to be determined. Clearly, uν=0 on Ω. We only need to check the following differential inequality

    0εm0Δv(x,t)+μεδ0(1ε0),xΩ,t>t0,

    which is valid if we further let

    ε0(μ2ΔvL(Ω×(t0,+)))1mδ,

    since δ<m and Δv is uniformly bounded according to Theorem 3.2. Applying the comparison principle Lemma 4.1 again, we find

    u(x,t)u_(x,t)ε0,xΩ,t>t0.

    This completes the proof.

    Remark 3. It is interesting to compare the self similar weak lower solution g(x,t) in the proof of Lemma 4.5 to the Barenblatt solution of porous medium equation

    B(x,t)=(1+t)k[(1k(m1)2mn|x|2(1+t)2k/n)+]1m1,

    with k=1/(m1+2/n). The Barenblatt solution B(x,t) is decaying at the rate (1+t)1/(m1+2/n) in L(Rn) and the support is expanding at the rate (1+t)2k/n. While the self similar weak lower solution g(x,t) is decaying at the rate (1+t)(1β)/(m1) and its support is expanding at the rate (1+t)β. Here in the proof we have selected β>0 sufficiently small, which means the support of g is expanding with a much slower rate and the maximum of g is decaying at a slightly faster rate.

    Proof of Theorem 2.3. This has been proved in Lemma 4.5.

    After proving the support expanding property of the first equation in (3), which is a degenerate diffusion equation, we can deduce the following convergence properties of all components.

    Lemma 4.6. Let (u,v,w,z) be a globally bounded weak solution of (3) with the first component initial data u00, u00 and 1δ<m. Then there exist constants C1,C2>0 and c1,c2>0 independent of t such that

    w(,t)L(Ω)+w(,t)L(Ω)C1ec1t,

    and

    v(,t)(¯v0+¯w0)L(Ω)+v(,t)L(Ω)+Δv(,t)L(Ω)C2ec2t,

    for all t>0, where ¯f=Ωfdx/|Ω|.

    Proof. Applying Lemma 4.3, we see that

    t0z(x,t)dsCt0Ωu(y,s)dydsCCtt0Ωu(y,s)dydsCC|Ω|ε0(tt0)Cc1tC,xΩ,t>t0,

    since u(x,t)ε0 for xΩ and t>t0 according to Lemma 4.5. Therefore,

    w(x,t)=w0(x)et0z(x,s)dsw0(x)ec1t+CC1ec1t,xΩ,t>t0. (29)

    This is also valid for t(0,t0) upon enlarging C1 if necessary and hereafter we only need to prove this lemma for t>t0. We also have

    |w(x,t)|=|w0(x)|et0z(x,s)ds+w0(x)et0z(x,s)ds|t0z(x,s)ds|Cec1t+Cec1ttC1ec1t,xΩ,t>t0,

    with 0<c1<c1. We may write C1 and c1 as C1 and c1 for simplicity. Therefore,

    |(wz)(x,t)||zw(x,t)|+|wz(x,t)|Cec1t,xΩ,t>t0,

    It follows form the second equation in (3) that

    v(x,t)=etΔv0+t0e(ts)Δ(wz)(,s)ds,t>0,

    and

    v(x,t)=etΔv0+t0e(ts)Δ(wz)(,s)ds,t>0,

    Using the standard LpLq type estimate for Δv, we get

    Δv(x,t)L(Ω)etΔ|v0|L(Ω)+t0e(ts)Δ|(wz)(x,s)|L(Ω)dsC(1+t12)eλ1tv0L(Ω)+Ct0(1+(ts)12)eλ1(ts)(wz)(,s)L(Ω)Ceλ1t+Ct0(1+(ts)12)eλ1(ts)ec1sdsC2ec2t,xΩ,t>t0,

    where λ1>0 is the first nonzero eigenvalue of Δ with homogeneous Neumann boundary condition. The L estimate of v can be deduced in a similar way. In the proof of Lemma 3.7, we have obtained

    Ω(v(x,t)+w(x,t))dxΩ(v0(x)+w0(x))dx,

    which is the same as the estimate of vε+wε. It follows from (29) that w(x,t) is decaying to zero exponentially. This implies that

    ¯v(t)=1|Ω|Ωv(x,t)dx

    is converging to ¯v0+¯w0 exponentially. A Poincaré type inequality shows

    v(x,t)¯v(t)L(Ω)Cv(x,t)L(Ω)Cec2t.

    Therefore,

    v(x,t)(¯v0+¯w0)L(Ω)v(x,t)¯v(t)L(Ω)+¯v(t)(¯v0+¯w0)L(Ω)v(x,t)¯v(t)L(Ω)+¯w(t)L(Ω)Cec2t,xΩ,t>t0,

    The proof is completed.

    Lemma 4.7. For constants C,c>0 and m>1, the local solution g of the following ODE

    {g(t)=Cectgm,t>0,g(0)=g0>0,

    blows up in finite time if c/C<(m1)gm10, while remains bounded if c/C>(m1)gm10.

    Proof. There holds

    1m1(1gm1)=Cect,t>0.

    Integrating over (0,t) shows

    1m1(1gm101gm1(t))=Cc(1ect).

    A simple analysis completes this proof.

    Lemma 4.8. Let (u,v,w,z) be a globally bounded weak solution of (3) with the first component initial data u00, u00 and 1δ<m. Then there exist constants C3>0 and c3>0 independent of t such that

    u(,t)1L(Ω)C3ec3t,

    for all t>0.

    Proof. Lemma 4.5 implies that u(x,t)ε0 for xΩ and t>t0. It suffices to prove this lemma for tt1 with some fixed t1t0 to be determined. We use upper and lower solution method to achieve this. Let u1(t) and u2(t) be one pair of the solutions of the following ODE

    {u1(t)um1Δv(,t)L(Ω)+μuδ1(1u1),u2(t)um2Δv(,t)L(Ω)+μuδ2(1u2),t>t1,u1(t1)u(,t1)L(Ω),u2(t1)ε0. (30)

    Lemma 4.1 shows that

    u1(t)u(x,t)u2(t),xΩ,t>t0.

    We only need to find one pair of (u1,u2) such that u1 and u2 both converge to 1 exponentially. A sufficient condition of (30) is

    {u1(t)=C2ec2tum1+μuδ1(1u1),u2(t)=C2ec2tum2+μuδ2(1u2),t>t1,u1(t1)=u(,t1)L(Ω)+1,u2(t1)=ε0, (31)

    since Δv(,t)L(Ω)C2ec2t according to Lemma 4.6. We note that we can choose t1 sufficiently large such that

    c2C2ec2t1>2(m1)(supt>0u(,t)L(Ω)+1)m1.

    Lemma 4.7 implies that u1(t) is uniformly bounded by some constant C. And a simple ODE comparison shows that u1(t)>1 for all t>t1. Therefore,

    {u1(t)CmC2ec2t+μεδ0(1u1),t>t1,u1(t1)=u(,t1)L(Ω)+1.

    We see that u1(t) is an upper solution of u(x,t) and an upper solution of u1(t) is ¯u1(t) such that

    {¯u1(t)=CmC2ec2t+μεδ0(1¯u1),t>t1,¯u1(t1)=u(,t1)L(Ω)+1, (32)

    which can be solved as

    ¯u1(t)=1+eμεδ0(tt1)(u(,t1)L(Ω)+1)+CmC2tt1eμεδ0(ts)ec2sdseμεδ0(tt1)1+eμεδ0(tt1)u(,t1)L(Ω)+CmC2Cemin{μεδ0,c2}t/2,t>t1.

    On the other hand, the lower solution of u(x,t) satisfies

    {u2(t)=C2ec2tum2+μuδ2(1u2),t>t1,u2(t1)=ε0.

    We note that we can choose t1 sufficiently large that

    C2ec2tεm0μεδ0(1ε0).

    An ODE comparison shows that ε0u2(t)<1 for all t>t1 and

    {u2(t)C2ec2t+μεδ0(1u2),t>t1,u2(t1)=ε0.

    We see that u2(t) is a lower solution of u(x,t) and a lower solution of u2(t) is u_2(t) such that

    {u_2(t)=C2ec2t+μεδ0(1u_2),t>t1,u_2(t1)=ε0.

    This can also be solved as

    u_2(t)=1+eμεδ0(tt1)ε0C2tt1eμεδ0(ts)ec2sdseμεδ0(tt1)1eμεδ0(tt1)C2Cemin{μεδ1,c2}t/2,t>t1.

    Thus, we conclude

    u_2(t)ut(t)u(x,t)ut(t)¯u1(t),t>t1,

    and u_2(t), ¯u1(t) converge to 1 exponentially.

    Lemma 4.9. Let (u,v,w,z) be a globally bounded weak solution of (3) with the first component initial data u00, u00 and 1δ<m. Then there exist constants C4>0 and c4>0 independent of t such that

    z(,t)1L(Ω)C4ec4t,

    for all t>0.

    Proof. From the fourth equation in (3), we have

    z(x,t)=et(Δ1)z0+t0e(ts)(Δ1))u(,s)ds,t>0.

    We note that

    t0e(ts)(Δ1))1ds=1et,

    which can be deduced by solving the ODE z=z+1 with z(0)=0. Therefore,

    z(x,t)1L(Ω)et(Δ1)z0L(Ω)+t0e(ts)(Δ1))(u(,s)1)L(Ω)ds+etCet(z0L(Ω)+1)+Ct0e(ts)(u(,s)1)L(Ω)dsCet+CC3t0e(ts)ec3sdsC4ec4t,t>0.

    The proof is completed.

    Proof of Theorem 2.4. This is proved by collecting Lemma 4.5, Lemma 4.6, Lemma 4.8 and Lemma 4.9.

    Finally, we construct a self similar upper solution with expanding support to prove Theorem 2.2. We note that for constructing a weak upper solution for the heat equation, one should replace the cut-off composite function ()+ by (). But here for the degenerate porous medium type equation and the self similar function of the form g=[(1|x|2)+]d with md>1, we can check that gm is continuous and ΔgmLq(Ω) for some q>1. This shows that the differential inequality for an upper solution only need to be valid almost everywhere, without the possible Radon measures on the boundary of its support.

    Lemma 4.10. Let (u,v,w,z) be a globally bounded weak solution of (3). We further assume that

    suppu0¯Br0(x0)Ω,

    for some r0>0 and x0Ω. Define a function

    g(x,t)=ε(τ+t)σ[(η|xx0|2(τ+t)β)+]d,xΩ,t0,

    where d=1/(m1), β>0, σ>0, ε>0, η>0, τ(0,1). Then by appropriately selecting β, σ ε, η and τ, the support of g(x,t) is contained in Ω for t(0,t0) with some t0>0 and the function g(x,t) can be an upper solution of the first equation in (3) on Ω×(0,t0), that is,

    {gtΔgm(gmv)+μgδ(1g),xΩ,t(0,t0),gν0,xΩ,t(0,t0),g(x,0)u0(x)0,xΩ,

    in the sense that the following inequality

    t00Ωgφtdxdt+Ωg(x,0)φ(x,0)dxt00Ωgmφdxdtt00Ωgmvφdxdtt00Ωμgδ(1g)φdxdt,

    holds for all test functions 0φL2((0,t0);W1,2(Ω))W1,2((0,t0);L2(Ω)) with φ(x,t0)=0 on Ω and g(x,0)u0(x)0 on Ω. Therefore, u(x,t)g(x,t) and there exist a family of monotone increasing open sets {A(t)}t(0,t0) such that

    suppu(,t)¯A(t)Ω,t(0,t0),

    and A(t) has a finite derivative with respect to t.

    Proof. For simplicity, we let

    h(x,t)=(η|xx0|2(τ+t)β)+,xΩ,t0,

    and

    A(t)={xΩ;|xx0|2(τ+t)β<η},t0.

    Since u0C(¯Ω) and suppu0¯Br0(x0)Ω, we see that there exist r1>r0 and ε1>0 such that Br1(x0)⊂⊂Ω and u0(x)ε1 for all xΩ. Without loss of generality, we may assume that x0=0. Straightforward computation shows that

    gt=σε(τ+t)σ1hd+ε(τ+t)σdhd1β|x|2(τ+t)β+1,gm=εm(τ+t)mσmdhmd12x(τ+t)β,Δgm=εm(τ+t)mσmd(md1)hmd24|x|2(τ+t)2βεm(τ+t)mσmdhmd12n(τ+t)β,

    for all xA(t) and t>0. Let τ(0,1) to be determined and

    r2=r0+r12,η=r22τβ,t0=min{τ,τ((r1r2)2β1)}. (33)

    According to the definition of g, we see that A(0)=Br2(x0), suppu0⊂⊂¯A(0)Ω, and A(t0)Br1(x0)⊂⊂Ω. Therefore, gν=0 and gmν=0 on Ω for all t(0,t0), and

    g(x,0)=ετσ[(η|xx0|2τβ)+]dετσ(r22τβr20τβ)d1Br0(x0)ε11Br0(x0)u0(x),xΩ,

    provided that

    ετσ(r22τβr20τβ)dε1. (34)

    In order to find a weak lower solution g, we only need to check the following differential inequality on A(t)

    gtΔgm(gmv)+μgδ(1g),xA(t),t(0,t0). (35)

    Since 0gεηd, we see that μgδ(1g)μgδ for all xΩ and t0. Further,

    |(gmv)|gm|Δv|+|mgm1||g||v|gmΔvL(Ω×R+)+(m+ετσηd)|gm|vL(Ω×R+).

    We denote C1=vL(Ω×R+) and C2=ΔvL(Ω×R+) for convenience, since they are bounded according to Theorem 3.2. A sufficient condition of inequality (35) is

    σε(τ+t)σ1hd+ε(τ+t)σdhd1β|x|2(τ+t)β+1+εm(τ+t)mσmdhmd12n(τ+t)βC2εm(τ+t)mσhmd+(m+ετσηd)C1εm(τ+t)mσmdhmd12|x|(τ+t)β+εm(τ+t)mσmd(md1)hmd24|x|2(τ+t)2β+μεδ(τ+t)δσhdδ, (36)

    for all xA(t) and t(0,t0). As we have chosen d=1/(m1), we rewrite (36) into

    σε(τ+t)σ1h+εβm1(τ+t)σ|x|2(τ+t)β+1+2nmm1εm(τ+t)mσh(τ+t)βC2εm(τ+t)mσh2+2(m+ετσηd)C1εm(τ+t)mσmdh|x|(τ+t)β+m(m1)2εm(τ+t)mσ4|x|2(τ+t)2β+μεδ(τ+t)δσhdδd+1,xA(t),t(0,t0).

    Let ε, β, σ and τ be chosen such that

    {12εβm1(τ+t)σ|x|2(τ+t)β+1m(m1)2εm(τ+t)mσ4|x|2(τ+t)2β,13σε(τ+t)σ1hC2εm(τ+t)mσh2,13σε(τ+t)σ1hμεδ(τ+t)δσhdδd+1,12εβm1(τ+t)σ|x|2(τ+t)β+1+13σε(τ+t)σ1h2(m+ετσηd)C1εm(τ+t)mσmdh|x|(τ+t)β,xA(t),t(0,t0). (37)

    We have the following estimate

    2(m+ετσηd)C1εm(τ+t)mσmdh|x|(τ+t)βm(m1)2εm(τ+t)mσ4|x|2(τ+t)2β+(m+ετσηd)2C21mεm(τ+t)mσh2,

    for all xA(t) and t(0,t0). Therefore, a sufficient condition of (37) is

    {(m1)β8mεm1(τ+t)(m1)σβ+1,2σ/3(C2+(m+ετσηd)2C21m)εm1(τ+t)(m1)σ+1h,σ/3μεδ1(τ+t)(δ1)σ+1hd(δ1),xA(t),t(0,t0). (38)

    We note that η, τ and t0 satisfy the condition (33) and (34), and then hη=r22/τβ, τ+tτ+t02τ, ετσdβ(r22r20)dε1. For τ(0,1), we choose

    ε=ε1τσdβ(r22r20)d:=C3τdβσ.

    Now, we only need to find τ(0,1) such that

    {(m1)β8mCm132max{0,(m1)σβ+1}τ,2σ/3(C2+(m+C3r2d2)2C21m)Cm132(m1)σ+1r22τ,σ/3μCδ132(δ1)σ+1r2d(δ1)2τ.

    This can be done by selecting β=1, σ=1, and τ(0,1) sufficiently small.

    The comparison principle Lemma 4.1 implies that u(x,t)g(x,t) for all xΩ and t(0,t0). Thus,

    suppu(,t)¯A(t)={xΩ;|xx0|2<η(τ+t)β},t(0,t0),

    and

    A(t)={xΩ;|xx0|=η12(τ+t)β2},t(0,t0),

    which has finite derivative with respect to t.

    Remark 4. Similar to the weak lower solution in Lemma 4.5, we compare the self similar weak upper solution g(x,t) in the proof of Lemma 4.10 to the Barenblatt solution of porous medium equation

    B(x,t)=(1+t)k[(1k(m1)2mn|x|2(1+t)2k/n)+]1m1,

    with k=1/(m1+2/n). The Barenblatt solution B(x,t) is decaying at the rate (1+t)1/(m1+2/n) in L(Rn) and the support is expanding at the rate (1+t)2k/n. As we have shown the support of the lower solution in Lemma 4.5 is expanding with a much slower rate and decaying at a slightly faster rate. Here, the upper solution is increasing at the rate (τ+t)σ and its support is expanding at the rate (τ+t)β. The increasing of g(x,t) makes it possible to be an upper solution, which can be seen from the proof.

    Remark 5. From the proof of Lemma 4.10, we can choose β>0 to be as small as we want. But we note that suppu0⊂⊂suppg(,0) and if we choose a smaller β>0, then the parameters τ and t0 are also smaller. This shows if we let the upper solution expands slower, then it may only be an upper solution for a smaller time interval. Thus, the slower expanding upper solution g(x,t) on a smaller time interval does not contradict to the possible feature that the solution u(x,t) expands at a fixed rate since suppu0⊂⊂suppg(,0) at the initial time.

    Proof of Theorem 2.2. This has been proved in Lemma 4.10.


    Appendix

    In this section, we extend the derivation of the classical taxis models in [36]. The derivation of the model begins with a master equation for a continuous-time and discrete-space random walk

    uit=T+i1ui1+Ti+1ui+1(T+i+Ti)ui, (39)

    where T±i() denote the transitional-probabilities per unit time of a one-step jump to i±1 and ui denotes the cell density at i.

    Painter and Hillen [11,28] proposed volume filling approach. In this model, the transitional probability then takes the form

    T±i=q(ui±1)(α+β(τ(vi±1)τ(vi))), (40)

    where q(u) denotes the probability of a cell finding space at its neighboring location, constant α is the intrinsic dispersion coefficient, constant β the coefficient signal detection, vi the signal concentration, and τ the mechanism of tactic responses in cell populations, such as chemotaxis, haptotaxis or phototaxis. Substituting (40) to the master equation (39), in the PDE limits they derives

    ut=(d1(q(u)q(u))uχ(v)q(u)uu)

    where d1=kα, χ(v)=2kβdτ(v)dv, k is a scaling constant. Note that q(u) is a non-increasing function in this model, which says that the probability of a cell finding space at its neighboring site decreases in the cell density at that site.

    Since a different combination of the above strategies may be necessary to reflect cell movement, we combine the local and gradient-based strategies and assume the transitional probability of the form

    T±i=q(ui)(α+β(τ(vi±1)τ(vi))), (41)

    where q(u) represents the jump probability of a cell due to the population pressure at present site. At the microscopic level, a high cell density results in increased probability of a cell being ''pushed'' from departure site [19,25,29], for example due to the pressure exerted by neighboring cells. We shall assume that only a finite number of cells, Umax, can be accommodated at any site. We study the relative density ˜u=u/Umax, (and drop the symbol ~ for simplicity). Moreover, the jump probability is 1 when the cell density exceeds Umax and it is zero when the cell density is zero. Thus we stipulate the following conditions on q:

    q(0)=0,q(1)=1andq(u)0,for all 0u1.

    A natural choice for q(u) is

    q(u)=um1,m>1, (42)

    which states that the probability of a jump leaving one site increases with the cell density at that site [24,37].

    Substituting (41) into the Master Equation (39) gives:

    ddtui=qi1(α+βi1(τiτi1))ui1+qi+1(α+βi+1(τiτi+1))ui+1qi(α+βi(τi+1τi))uiqi(α+βi(τi1τi))ui=α(qi1ui1+qi+1ui+12qiui)+βi1qi1(τiτi1)ui1+βi+1qi+1(τiτi+1)ui+1βiqi(τi+1+τi12τi)ui=α(qi1ui1+qi+1ui+12qiui)βi+1qi+1ui+1(τi+1τi)+βiqiui(τiτi1)(βiqiui(τi+1τi)βi1qi1ui1(τiτi1))=α(qi1ui1+qi+1ui+12qiui)((βi+1qi+1ui+1+βiqiui)(τi+1τi)(βi1qi1ui1+βiqiui)(τiτi1)).

    We set x=kh, interpret x as a continuous variable and extend the definition of ui accordingly. The transitional probabilities of jumping to a neighboring location depend on the spatial scale h. Thus we assume that T±h=kh2T± for some scaling constant k. Expanding the right-hand side with respect to h, we obtain for the cell density u(x,t):

    ut=k(α2(q(u)u)x22x(βq(u)uτx))+O(h2).

    By taking the limit of h0, we arrive at the following model

    ut=Du2(q(u)u)x2x(βχ(v)q(u)uvx),

    where Du=kα, χ(v)=2kdτ(v)dv. The function χ(v) is commonly referred as the tactic sensitivity function. The simplest form is χ(v)=χ0 with χ0 being a constant.

    Apart from that, we consider a modification of the Verhulst logistic growth term to model organ size evolution introduced by Blumberg [2] and Turner [41], which is called hyper-logistic function, accordingly

    f(u)=ruδ(1μu).

    Including cell kinetics and signal dynamics, we derive the resulting model for the cell movement

    ut=DuΔ(q(u)u)dispersionχ0(q(u)uv)chemotaxis+μuδ(1ru)proliferation.

    Incorporating the kinetic equation of ECM and MDE, we arrive at a modified Chaplain and Lolas' chemotaxis model, see (3), where we assume the constants Du,χ0,r=1 for simplification.


    Acknowledgments

    The authors would like to express their sincere thanks to two anonymous referees for their valuable comments and suggestions, which led an important and significant improvement of the paper. The research of S. Ji is supported by NSFC Grant No. 11701184. The research of C. Jin was supported in part by NSFC grant No. 11471127, Guangdong Natural Science Funds for Distinguished Young Scholar Grant No. 2015A030306029, the Excellent Young Professors Program of Guangdong Province Grant No. HS2015007, and Special Support Program of Guangdong Province of China. The research of M. Mei was supported in part by NSERC Grant RGPIN 354724-16, and FRQNT Grant No. 192571. The research of J. Yin was supported in part by NSFC Grant No. 11771156.


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