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Int J Med Sci 2014; 11(1):7-16. doi:10.7150/ijms.6851 This issue Cite

Research Paper

17β-Estradiol Inhibits Mesenchymal Stem Cells-Induced Human AGS Gastric Cancer Cell Mobility via Suppression of CCL5- Src/Cas/Paxillin Signaling Pathway

Chao-Hung Kuo^1,2,3, Chung-Jung Liu^1,2, Chien-Yu Lu^1,3, Huang-Ming Hu¹, Fu-Chen Kuo⁴, Yu-Sen Liou¹, Yuan-Chieh Yang⁵, Ming-Chia Hsieh^6,7, Oscar K. Lee^8,9, Deng-Chyang Wu^1,2,3,10, Sophie S.W. Wang^1,2#✉, Yao-Li Chen^11,12#✉

1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
2. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3. Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4. School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
5. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
6. Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
7. Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
8. Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan
9. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
10. Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
11. Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
12. School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
# These authors contributed equally to this paper.

✉ Corresponding authors: Yao-Li Chen, MD; Department of General Surgery, Changhua Christian Hospital, and School of Medicine, Kaohsiung Medical University, No. 135 Nan-Hsiao Street, Changhua City, Changhua County 500, Taiwan. Tel: +88647238595 ext4751 e-mail: 31560org.tw and Sophie S.W. Wang, MD, PhD; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, Kaohsiung City, 807 Taiwan Tel: + 88673121101ext7451; Fax: +88673135612 E-mail:swang910com More

Abstract

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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