Endocan reduces the malign grade of gastric cancer cells by regulating associated protein expression

Tumor Biology - Tập 37 - Trang 14915-14921 - 2016
Zhang Sumei1, Chen Shaolong1, Wei Xiang1, Qi Yinliang1,2, Zhou Qing1, Wang Yuan1
1Laboratory of Molecular Biology and Department of Biochemistry, Key Laboratory of Gene Research of Anhui Province, Hefei, People’s Republic of China
2General Department of Hyperbaric Oxygen, The Second People’s Hospital of Hefei, Hefei, China

Tóm tắt

Endocan, which has been identified to be low expressed in gastric cancer, was found to be positively related to the differentiation level of gastric cancer in vivo and in vitro. In the present study, we aimed to investigate the role of endocan in gastric adenocarcinoma cell line SGC7901 by artificially upregualting or downregulating endocan expression using endocan recombinant vector or specific small interfering RNA (siRNA)-targeting endocan gene, respectively. The effects of endocan recombinant vector-mediated over-expressing and siRNA-mediated endocan silencing on the differentiation, migration, and apoptosis of SGC7901 cells were assessed. Furthermore, the primary molecular mechanisms of endocan were explored by testing the expression alterations of associated protein in SGC7901 along endocan over-expression or knockdown. We found that over-expression of endocan reduced the migration but promoted the differentiation and apoptosis of SGC7901 cells. While, knockdown of endocan did just the opposite. Some molecules were found to participate in endocan-mediated anti-tumor effects, such as p53, caspase 3, and MMP-9. In conclusion, our findings suggest that endocan plays an anti-carcinogenic role in gastric cancer development and progression and might serve as a prognostic biomarker as well as a potential therapeutic target for gastric cancer.

Tài liệu tham khảo

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. Chen W, Zheng R, Zhang S, Zhao P, Li G, Wu L, et al. The incidences and mortalities of major cancers in China, 2009. Chin J Cancer. 2013;32:106–12. Zhang SM, Zuo L, Gui SY, Zhou Q, Wei W, Wang Y. Induction of cell differentiation and promotion of endocan gene expression in stomach cancer by melatonin. Mol Biol Rep. 2012;39:2843–9. Lassalle P, Molet S, Janin A, Heyden JV, Tavernier J, Fiers W, et al. ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines. J Biol Chem. 1996;271:20458–64. Bechard D, Gentina T, Delehedde M, Scherpereel A, Lyon M, Aumercier M, et al. Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. J Biol Chem. 2001;276:48341. Miao Y, Zong M, Jiang T, Yuan X, Guan S, Wang Y, et al. A comparative analysis of ESM-1 and vascular endothelial cell marker (CD34/CD105) expression on pituitary adenoma invasion. Pituitary. 2016;19:194–201. Ozaki K, Toshikuni N, George J, Minato T, Matsue Y, Arisawa T, et al. Serum endocan as a novel prognostic biomarker in patients with hepatocellular carcinoma. J Cancer. 2014;5:221–30. Abid MR, Yi X, Yano K, Shih SC, Aird WC. Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res. 2006;72:136–45. Grigoriu BD, Depontieu F, Scherpereel A, Gourcerol D, Devos P, Ouatas T, et al. Endocan expression and relationship with survival in human nonsmall cell lung cancer. Clin cancer res off J Am Assoc. Cancer Res. 2006;12:4575–82. Cornelius A, Cortet-Rudelli C, Assaker R, Kerdraon O, Gevaert MH, Prevot V, et al. Endothelial expression of endocan is strongly associated with tumor progression in pituitary adenoma. Brain Pathol. 2012;22:757–64. Maurage CA, Adam E, Mineo JF, Sarrazin S, Debunne M, Siminski RM, et al. Endocan expression and localization in human glioblastomas. J Neuropathol Exp Neurol. 2009;68:633–41. Rennel E, Mellberg S, Dimberg A, Petersson L, Botling J, Ameur A, et al. Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer. Exp Cell Res 2007; 313: 1285–1294. Xu Z, Zhang SM, Zhou Q, Wang Y, Xia RX. Endocan, a potential prognostic and diagnostic biomarker of acute leukemia. Mol Cell Biochem 2014; 395: 117–123. Zuo L, Lu M, Zhou Q, Wei W, Wang Y. Butyrate suppresses proliferation and migration of RKO colon cancer cells though regulating endocanexpression by MAPK signaling pathway. Food Chem Toxicol. 2013;62:892–900. Zuo L, Zhang SM, RL H, Zhu HQ, Zhou Q, Gui SY, et al. Correlation between expression and differentiation of endocan in colorectal cancer. World J Gastroenterol. 2008;14(28):4562–8. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2:563–72. Zhang SM, Qi YL, Zhang HT, He W, Zhou Q, Gui SY, et al. Melatonin inhibits cell growth and migration,but promotes apoptosis in gastric cancer cell line, SGC7901. Biotech Histochem. 2013;88(6):281–9. Leroy X, Aubert S, Zini L, Franquet H, Kervoaze G, Villers A, et al. Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma. Histopathology. 2010;56:180–7. Hatfield KJ, Lassalle P, Leiva RA, Lindås R, Wendelboe Ø, Bruserud Ø. Serum levels of endothelium-derived endocan are increased in patients with untreated acute myeloid leukemia. Hematology. 2011;16:351–6. Bao L, Liu F, Guo HB, Li Y, Tan BB, Zhang WX, et al. Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway. Tumour Biol. 2016; [Epub ahead of print]. Sampieri CL, de la Peña S, Ochoa-Lara M, Zenteno-Cuevas R, León-Córdoba K. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis. World J Gastroenterol. 2010;16:1500–5. Fields GB. New strategies for targeting matrix metalloproteinases. Matrix Biol 2015; 44–46:239–246. Major apoptotic mechanisms and genes involved in apoptosis. Kiraz Y, Adan A, Kartal Yandim M, Baran Y. Tumour Biol. 2016 Apr 9.