title: Stromal cells of endometrial carcinoma promotes proliferation of epithelial cells through the HGF/c-Met/Akt signaling pathway.
abstract: Tumor microenvironment participates in the endometrial carcinoma pathogenesis. This study focuses on the interaction between endometrial cancer stromal cells and epithelial cells from normal endometrium tissue using in vitro transwell coculture system and in vivo xenograft model. We demonstrate that cancer interstitial (CI) cells stimulate normal epithelial (NE) cell proliferation. Tumor xenograft model confirmed the pro-proliferative effect of CI cells on epithelial cell growth. Tumor suppressor PTEN was reduced, and oncogene K-ras was increased in epithelial cells cocultured with CI cells. Moreover, we observed increased expression of hepatocyte growth factor (HGF) in CI cells and tumor xenografts derived from the coculturing system. Higher HGF secretion activated Akt signaling pathway, which was reversed by HGF receptor inhibitor (crizotinib). These results demonstrate that endometrial carcinoma stromal cells stimulate epithelial cell proliferation via the HGF/c-Met/Akt signaling pathway.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xin
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.forename: Teng
authors.initials: T
authors.lastname: Hua
authors.forename: Hongbin
authors.initials: H
authors.lastname: Wang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018920:Coculture Techniques; D000077547:Crizotinib; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D015398:Signal Transduction / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C066855:HGF protein, human; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D051058:Oncogene Protein v-akt