22 March 2018
Int J Med Sci 2014; 11(1):7-16. doi:10.7150/ijms.6851
17β-Estradiol Inhibits Mesenchymal Stem Cells-Induced Human AGS Gastric Cancer Cell Mobility via Suppression of CCL5- Src/Cas/Paxillin Signaling Pathway
1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17β-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17β-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17β-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.
Keywords: Estrogen, Mesenchymal stem cell, Human gastric cancer cell, CCL-5, Cell mobility
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How to cite this article:
Kuo CH, Liu CJ, Lu CY, Hu HM, Kuo FC, Liou YS, Yang YC, Hsieh MC, Lee OK, Wu DC, Wang SSW, Chen YL. 17β-Estradiol Inhibits Mesenchymal Stem Cells-Induced Human AGS Gastric Cancer Cell Mobility via Suppression of CCL5- Src/Cas/Paxillin Signaling Pathway. Int J Med Sci 2014; 11(1):7-16. doi:10.7150/ijms.6851. Available from http://www.medsci.org/v11p0007.htm