Modeling of pH regulation in tumor cells: Direct interaction between proton-coupled lactate transporters and cancer-associated carbonicanhydrase

Sandesh Athni Hiremath; Christina Surulescu; Somayeh Jamali; Samantha Ames; Joachim W. Deitmer; Holger M. Becker; Sandesh Athni Hiremath; Christina Surulescu; Somayeh Jamali; Samantha Ames; Joachim W. Deitmer; Holger M. Becker

doi:10.3934/mbe.2019016

Mathematical Biosciences and Engineering

2019, Volume 16, Issue 1: 320-337. doi: 10.3934/mbe.2019016

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Research article

Modeling of pH regulation in tumor cells: Direct interaction between proton-coupled lactate transporters and cancer-associated carbonicanhydrase

1.
Technische Universität Kaiserslautern (TUK) Felix-Klein-Zentrum für Mathematik Paul-Ehrlich-Str. 31, 67663 Kaiserslautern, Germany
2.
Technische Universität Kaiserslautern (TUK), Division of General Zoology, Department of Biology, Erwin-Schrödinger-Str. 13, 67663 Kaiserslautern, Germany
3.
University of Veterinary Medicine Hannover, Institute of Physiological Chemistry, Bünteweg 17, 30559 Hannover, Germany

Received: 07 March 2018 Accepted: 21 August 2018 Published: 13 December 2018

The most aggressive tumor cells, which often reside in a hypoxic environment, can release vast amounts of lactate and protons via monocarboxylate transporters (MCTs). This additional proton efflux exacerbates extracellular acidification and supports the formation of a hostile environment. In the present study we propose a novel, data-based model for this proton-coupled lactate transport in cancer cells. The mathematical settings involve systems coupling nonlinear ordinary and stochastic differential equations describing the dynamics of intra- and extracellular proton and lactate concentrations. The data involve time series of intracellular proton concentrations of normoxic and hypoxic MCF-7 breast cancer cells. The good agreement of our final model with the data suggests the existence of proton pools near the cell membrane, which can be controlled by intracellular and extracellular carbonic anhydrases to drive proton-coupled lactate transport across the plasma membrane of hypoxic cancer cells.
- dynamic buffer capacity,
- two-compartment model,
- stochastic differential equations,
- numerical simulations
Citation: Sandesh Athni Hiremath, Christina Surulescu, Somayeh Jamali, Samantha Ames, Joachim W. Deitmer, Holger M. Becker. Modeling of pH regulation in tumor cells: Direct interaction between proton-coupled lactate transporters and cancer-associated carbonicanhydrase[J]. Mathematical Biosciences and Engineering, 2019, 16(1): 320-337. doi: 10.3934/mbe.2019016

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Abstract

The most aggressive tumor cells, which often reside in a hypoxic environment, can release vast amounts of lactate and protons via monocarboxylate transporters (MCTs). This additional proton efflux exacerbates extracellular acidification and supports the formation of a hostile environment. In the present study we propose a novel, data-based model for this proton-coupled lactate transport in cancer cells. The mathematical settings involve systems coupling nonlinear ordinary and stochastic differential equations describing the dynamics of intra- and extracellular proton and lactate concentrations. The data involve time series of intracellular proton concentrations of normoxic and hypoxic MCF-7 breast cancer cells. The good agreement of our final model with the data suggests the existence of proton pools near the cell membrane, which can be controlled by intracellular and extracellular carbonic anhydrases to drive proton-coupled lactate transport across the plasma membrane of hypoxic cancer cells.

References

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