title: Suppression of IL-8-Src signalling axis by 17β-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.
abstract: Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17β -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17β-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17β-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis 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: Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
authors.forename: Chiu-Lin
authors.initials: CL
authors.lastname: Wang
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.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Sophie S W
authors.initials: SS
authors.lastname: Wang
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: Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
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: Chien-Yu
authors.initials: CY
authors.lastname: Lu
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 Ta-Tung Hospital, Kaohsiung, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D050719:Crk-Associated Substrate Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051419:Paxillin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology
chemical_list: C508606:CXCL8 protein, human; D050719:Crk-Associated Substrate Protein; D016209:Interleukin-8; C496061:PXN protein, human; D051419:Paxillin; D004958:Estradiol; D016392:Proto-Oncogene Proteins pp60(c-src); D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4
keywords: 17β-estradiol; IL-8; Src; cell invasion motility; gastric cancer; mesenchymal stem cell