title: 17β-estradiol inhibits mesenchymal stem cells-induced human AGS gastric cancer cell mobility via suppression of CCL5- Src/Cas/Paxillin signaling pathway.
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.
authors.affiliation: 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.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: 1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan ; 2. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: 1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan ; 3. Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lu
authors.affiliation: 1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Huang-Ming
authors.initials: HM
authors.lastname: Hu
authors.affiliation: 4. School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Fu-Chen
authors.initials: FC
authors.lastname: Kuo
authors.affiliation: 1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Liou
authors.affiliation: 5. Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yuan-Chieh
authors.initials: YC
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Ming-Chia
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: 8. Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan ; 9. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Oscar K
authors.initials: OK
authors.lastname: Lee
authors.affiliation: 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 ; 10. Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.affiliation: 1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan ; 2. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Sophie S W
authors.initials: SS
authors.lastname: Wang
authors.affiliation: 11. Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan ; 12. School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yao-Li
authors.initials: YL
authors.lastname: Chen
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D050719:Crk-Associated Substrate Protein; D004791:Enzyme Inhibitors; C496061:PXN protein, human; D051419:Paxillin; D004958:Estradiol; D019061:src-Family Kinases
keywords: CCL-5; Cell mobility; Estrogen; Human gastric cancer cell; Mesenchymal stem cell