The Role of extracellular matrix proteins in gastric cancer development via epithelial-mesenchymal transition
Gastroenterology and Hepatology from Bed to Bench,
,
9 December 2020
https://doi.org/10.22037/ghfbb.v13i1.2211
Abstract
Background: Gastric cancer (GC) is one of the most incident gastrointestinal cancers with high rate of mortality. Metastasis is one of the most challenging problems in gastric cancer treatment. Epithelial mesenchymal transition (EMT) of cancer cells is a complicated process controlled by different cells and molecular pathways which is considered as an important step in metastasis beginning.
Objectives: Due to finding better perception from environment of EMT, we evaluated the expression of some candidate extra cellular matrix (ECM) proteins including of THBS2, OSMR and CHI3L1 which were collected from RNA-seq bioinformatic analyses in our studies.
Materials and methods: AGS gastric cancer cell line was cultured and treated by TGF-β. EMT induction was verified by measuring expression of E-cadherin, Snail, β-catenin and Vimentin genes by real time PCR. Then, in following of our previous study, we evaluated expression of THBS2, OSMR and CHI3L1 genes in EMT induced cells by real time PCR
Results: Downregulation of E-cadherin and upregulation of Snail, β-catenin and Vimentin genes were verified in AGS treated cells in comparison with none-treated cells (P-value = 0.0355, P-value = 0.007, P-value = 0.0059, P-value = 0.0206 respectively). Also, Upregulation of THBS2, OSMR and CHI3L1 were validated in these cells after EMT induction (P-value = 0.0147, P-value = 0.05, P-value = 0.05 respectively).
Conclusion: Our morphological and molecular results validated EMT induction by TGF- β cytokine in AGS gastric cancer cell line. Furthermore, significant upregulation of candidate genes including of THBS2, OSMR and CHI3L1 verified the role of these proteins in gastric cancer invasiveness. However, further studies are needed for validation of prognostic value of these markers.
- Key words: Gastric cancer (GC), Epithelial mesenchymal transition (EMT), TGF- β cytokine, THBS2, OSMR and CHI3L1
References
2. Cheng XJ, Lin JC, Tu SP. Etiology and Prevention of Gastric Cancer. Gastrointest Tumors. 2016;3(1):25–36.
3. Norman A. On the origin of cancer foci. Cancer. 1952;5(3):581–2.
4. Yeung KT, Yang J. Epithelial – mesenchymal transition in tumor metastasis. 2017;11:28–39.
5. Tzanakakis G, Kavasi R, Voudouri K, Berdiaki A, Spyridaki I, Tsatsakis A, et al. Role of the Extracellular Matrix in Cancer-Associated Epithelial to Mesenchymal Transition Phenomenon. 2018;368–81.
6. Lamouille S, Xu J, Derynck R. Fakultas Psikologi Dan Sosial Budaya Universitas Islam Indonesia Yogyakarta. Nat Rev Mol Cell Biol. 2014;15(3):178–96.
7. Škovierová H, Okajčeková T, Strnádel J, Vidomanová E, Halašová E. Molecular regulation of epithelial-to-mesenchymal transition in tumorigenesis (Review). Int J Mol Med. 2018;41(3):1187–200.
8. Chia NY, Tan P. Molecular classification of gastric cancer. Ann Oncol. 2016;27(5):763–9.
9. Xu J, Lamouille S, Derynck R. TGF-β-induced epithelial to mesenchymal transition. 2009;19(2):156–72.
10. Hao Y, Baker D, Dijke P Ten. TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. Int J Mol Sci. 2019;20(11).
11. Abed S, Baghaei K, Pakzad P, Hashemi M, Zali MR. Evaluation of epithelial-mesenchymal transition genes involved in iranian gastric cancer patients via transcriptome analysis. Int J Cancer Manag. 2019;12(12).
12. Berlth F, Bollschweiler E, Drebber U, Hoelscher AH, Moenig S. Pathohistological classification systems in gastric cancer: Diagnostic relevance and prognostic value. World J Gastroenterol. 2014;20(19):5679–84.
13. Roche J. The epithelial-to-mesenchymal transition in cancer. Cancers (Basel). 2018;10(2):10–3.
14. Santos Ramos F, Wons L, João Cavalli I, M.S.F. Ribeiro E. Epithelial-mesenchymal transition in cancer: An overview. Integr Cancer Sci Ther. 2017;4(3):1–5.
15. Wang X, Zhang L, Li H, Sun W, Zhang H, Lai M. THBS2 is a Potential Prognostic Biomarker in Colorectal Cancer. Nat Publ Gr [Internet]. 2016; Available from: http://dx.doi.org/10.1038/srep33366
16. Physiology C. Expression Levels as Predictors of Gastric Cancer Prognosis. 2016;100700:1316–24.
17. Wendt MK, Balanis N, Carlin CR, Schiemann WP. STAT3 and epithelial–mesenchymal transitions in carcinomas. Jak-Stat. 2014;3(2):e28975.
18. Yu Z, Li Z, Wang C, Pan T, Chang X, Wang X, et al. Oncostatin M receptor, positively regulated by SP1, promotes gastric cancer growth and metastasis upon treatment with Oncostatin M. Gastric Cancer [Internet]. 2019;22(5):955–66. Available from: http://dx.doi.org/10.1007/s10120-019-00934-y
19. El-fattah AAA, Abdel N, Sadik H, Shaker OG, Kamal AM. Review Article Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk. 2018;2018(Figure 3).
20. Qiu Q, Wang L, Jin S, Liu G, Liu J, Ma L, et al. CHI3L1 promotes tumor progression by activating TGF- β signaling pathway in hepatocellular carcinoma. 2018;(June):1–12.
21. Geng B, Pan J, Zhao T, Ji J, Zhang C, Che Y, et al. Chitinase 3-like 1-CD44 interaction promotes metastasis and epithelial-to- mesenchymal transition through β -catenin / Erk / Akt signaling in gastric cancer. 2018;1–20.
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