The relationship between mouse lung adenocarcinoma at different stages and the expression level of exosomes in serum

Yanping Xie; Zhaohui Dong; Junhua Du; Xiaoliang Zang; Huihui Guo; Min Liu; Shengwen Shao; Yanping Xie; Zhaohui Dong; Junhua Du; Xiaoliang Zang; Huihui Guo; Min Liu; Shengwen Shao

doi:10.3934/mbe.2020080

Mathematical Biosciences and Engineering

2020, Volume 17, Issue 2: 1548-1557. doi: 10.3934/mbe.2020080

Previous Article Next Article

Research article Special Issues

The relationship between mouse lung adenocarcinoma at different stages and the expression level of exosomes in serum

1.
Department of Respiration, The First Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang 313000, China
2.
Department of Intensive Care Unit, The First Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Zhejiang 313000, China
3.
Key Laboratory for Translational Medicine, The First Hospital of Huzhou, First Affiliated Hospital, Huzhou University, Zhejiang 313000, China
4.
Institute of Microbiology and Immunology, Huzhou University, Zhejiang 313000, China

Received: 31 May 2019 Accepted: 20 November 2019 Published: 04 December 2019

Objective The purpose of this study is to investigate the relationship between N-methylN'-nitro-N-nitrosoguanidine (MNNG)-induced lung adenocarcinoma mouse of different stages and the level of exosomes in serum.

Methods Fifty KM mice (4 weeks old, weighing 18-22 g, female) were selected for experiment. MNNG was applied to induce lung adenocarcinoma in mice for model establishment. HE staining method was used to observe pathological changes of lung tissues. Exosomes in serum were extracted, and observed under a Transmission Electron Microscopy (TEM). Western blot was employed to examine the protein levels of exosome markers TSG101 and CD63.

Results HE staining results suggested MNNG-induced lung adenocarcinoma model mice were successfully constructed. The morphology of exosomes in serum of mouse model was observed under an Electron Microscopy, showing clear membrane structures presenting as saucer or concave hemisphere. In addition, the protein level of exosome marker CD63 in advanced mouse model was significantly up-regulated relative to that in the control group. Meanwhile, the expression of exosome marker protein TSG101 was found to be markedly increased in mouse models by comparison with that in control cases.

Conclusion In lung adenocarcinoma model mice, the occurrence and development of lung adenocarcinoma are greatly correlated with the expression level of exosomes in serum, which provides theoretical basis for the diagnosis of pathological staging of lung adenocarcinoma by exosomes.
- lung adenocarcinoma,
- exosome,
- MNNG-induced model,
- KM mouse
Citation: Yanping Xie, Zhaohui Dong, Junhua Du, Xiaoliang Zang, Huihui Guo, Min Liu, Shengwen Shao. The relationship between mouse lung adenocarcinoma at different stages and the expression level of exosomes in serum[J]. Mathematical Biosciences and Engineering, 2020, 17(2): 1548-1557. doi: 10.3934/mbe.2020080

Related Papers:

Abstract

Objective The purpose of this study is to investigate the relationship between N-methylN'-nitro-N-nitrosoguanidine (MNNG)-induced lung adenocarcinoma mouse of different stages and the level of exosomes in serum.

Methods Fifty KM mice (4 weeks old, weighing 18-22 g, female) were selected for experiment. MNNG was applied to induce lung adenocarcinoma in mice for model establishment. HE staining method was used to observe pathological changes of lung tissues. Exosomes in serum were extracted, and observed under a Transmission Electron Microscopy (TEM). Western blot was employed to examine the protein levels of exosome markers TSG101 and CD63.

Results HE staining results suggested MNNG-induced lung adenocarcinoma model mice were successfully constructed. The morphology of exosomes in serum of mouse model was observed under an Electron Microscopy, showing clear membrane structures presenting as saucer or concave hemisphere. In addition, the protein level of exosome marker CD63 in advanced mouse model was significantly up-regulated relative to that in the control group. Meanwhile, the expression of exosome marker protein TSG101 was found to be markedly increased in mouse models by comparison with that in control cases.

Conclusion In lung adenocarcinoma model mice, the occurrence and development of lung adenocarcinoma are greatly correlated with the expression level of exosomes in serum, which provides theoretical basis for the diagnosis of pathological staging of lung adenocarcinoma by exosomes.

References

[1]	C. Fitzmaurice, D. Dicker, A. Pain, H. Hamavid, The Global Burden of Cancer 2013, JAMA Oncol., 1 (2015), 505-527.
[2]	J. R. Molina, P. Yang, S. D. Cassivi, S. E. Schild, A. A. Adjei, Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship, Mayo Clin. Proc., 83 (2008), 584-594.
[3]	J. Xiao, A. Liu, X. Lu, X. Chen, W. Li, S. He, Prognostic significance of TCF21 mRNA expression in patients with lung adenocarcinoma, Sci. Rep., 7 (2017), 2027.
[4]	Z. Chen, C. M. Fillmore, P. S. Hammerman, C. F. Kim, K. K. Wong, Non-small-cell lung cancers: a heterogeneous set of diseases, Nat. Rev. Cancer, 14 (2014), 535-546.
[5]	D. S. Ettinger, Ten years of progress in non-small cell lung cancer, J. Natl. Compr. Cancer Network, 10 (2012), 292-295.
[6]	F. Ding, D. Wang, X. K. Li, L. Yang, H. Y. Liu, W. Cui, Overexpression of S100A14 contributes to malignant progression and predicts poor prognosis of lung adenocarcinoma, Thorac. Cancer, 9 (2018), 827-835.
[7]	Z. Sun, L. Wang, L. Dong, X. Wang, Emerging role of exosome signalling in maintaining cancer stem cell dynamic equilibrium, J. Cell Mol. Med., 22 (2018), 3719-3728.
[8]	J. Lotvall, H. Valadi, Cell to cell signalling via exosomes through esRNA, Cell Adh. Migr., 1 (2007), 156-158.
[9]	H. G. Zhang, W. E. Grizzle, Exosomes: A novel pathway of local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions, Am. J. Pathol., 184 (2014), 28-41.
[10]	C. Lässer, V. S. Alikhani, K. Ekström, M. Eldh, P. T. Paredes, Apostolos, Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages, J. Transl. Med., 9 (2011).
[11]	W. Li, C. Li, T. Zhou, X. Liu, X. Liu, X. Li, Role of exosomal proteins in cancer diagnosis, Mol. Cancer, 16 (2017), 145.
[12]	T. L. Whiteside, Exosomes carrying immunoinhibitory proteins and their role in cancer, Clin. Exp. Immunol., 189 (2017), 259-267.
[13]	M. Tomasetti, W. Lee, L. Santarelli, J. Neuzil, Exosome-derived microRNAs in cancer metabolism: Possible implications in cancer diagnostics and therapy, Exp. Mol. Med., 49 (2017).
[14]	C. F. Ruivo, B. Adem, M. Silva, S. A. Melo, The Biology of Cancer Exosomes: Insights and New Perspectives, Cancer Res., 77 (2017), 6480-6488.
[15]	D. Y. Luo, Inhibitory effect of refined Amorphophallus konjac on MNNG-induced lung cancers in mice, Chi. J. Oncol., 14 (1992), 48-50.
[16]	C. Sheridan, Exosome cancer diagnostic reaches market, Nat. Biotechnol., 34 (2016), 359-360.
[17]	M. Fabbri, A. Paone, F. Calore, R. Galli, E. Gaudio, R. Santhanam, MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response, Proc. Natl. Acad. Sci., 109 (2012), 2110-2116.
[18]	Y. Zhang, L. Duan, X. Xiang, Y. Huang, K. Qian, Y. Jiang, Levels of activation markers of platelets in peripheral blood and their significance in patients with lung cancer, Chi. J. Lung Cancer, 10 (2007), 216-218.
[19]	F. Liu, Y. Yu, Y. Jin, S. Fu, TSG101, identified by screening a cancer cDNA library and soft agar assay, promotes cell proliferation in human lung cancer, Mol. Biol. Rep., 37 (2010), 2829-2838.

Reader Comments

Your name:*

Email:*
© 2020 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)