title: 17β-Estradiol inhibition of IL-6-Src and Cas and paxillin pathway suppresses human mesenchymal stem cells-mediated gastric cancer cell motility.
abstract: Epidemiological studies demonstrate that the incidence and mortality of gastric cancer in women are lower than in men worldwide. Many studies have reported the delayed menopause and hormone replacement therapy are associated with a reduced risk for gastric cancer. It has been reported that endogenous estrogen lowers gastric cancer incidence in women, and cancer patients treated with estrogens have a lower subsequent risk of gastric cancer. It has been reported that estrogen decreases the progression of gastric cancer by inhibiting erbB-2 oncogene expression. Overexpression of estrogen receptor might inhibit the proliferation and invasion of MKN28 gastric cancer cells. Accumulating evidence suggests that bone marrow mesenchymal stem cells contribute to the progression of gastric cancer. However, it is unknown if 17β-estradiol (E2) treatment is sufficient to inhibit human bone marrow mesenchymal stem cells (HBMMSCs)-mediated cell motility in human gastric cancer cells. The results from human cytokine arrays have shown that HBMMSCs notably secrete interleukin 6 (IL-6) protein. Administration of IL-6-specific neutralizing antibody significantly inhibits HBMMSCs-mediated motility activity in human gastric cancer cells. Treatment of recombinant IL-6 soluble protein confirmed the role of IL-6 in mediating HBMMSCs-upregulated cell motility. IL-6 mainly upregulates motility activity via activation of Src signaling pathway in human gastric cancer cells. We further observed that E2 treatment inhibits HBMMSCs-induced cellular motility via suppressing the activation of IL-6-Src/Cas/paxillin signaling pathway in human gastric cancer cells. Collectively, these results suggest that E2 treatment significantly inhibits HBMMSCs-induced cellular motility in human gastric cancer cells.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Fu-Chen
authors.initials: FC
authors.lastname: Kuo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Huang-Ming
authors.initials: HM
authors.lastname: Hu
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Radiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chiao-Yun
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yaw-Bin
authors.initials: YB
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Kuang-Hung
authors.initials: KH
authors.lastname: Cheng
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Kazunari K
authors.initials: KK
authors.lastname: Yokoyama
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Department of Chemistry and Center for Nanoscience and Nanotechnology, National Sun Yat-sen University, Kaohsiung Taiwan.
authors.forename: Shuchen
authors.initials: S
authors.lastname: Hsieh
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: kjh88kmu@gmail.com.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuo
mesh_terms: D000906:Antibodies / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000906:Antibodies; D050719:Crk-Associated Substrate Protein; D015850:Interleukin-6; D051419:Paxillin; D004958:Estradiol; D016392:Proto-Oncogene Proteins pp60(c-src)