Tumor Biology

, Volume 36, Issue 8, pp 6239–6248 | Cite as

Stromal cells of endometrial carcinoma promotes proliferation of epithelial cells through the HGF/c-Met/Akt signaling pathway

  • Min Li
  • Xiaoyan Xin
  • Tingting Wu
  • Teng Hua
  • Hongbin Wang
  • Hongbo Wang
Research Article


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.


Endometrial carcinoma Tumor microenvironment HGF Akt signaling pathway 


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.South Branch of the Six People’s Hospital Affiliated to Shanghai Jiao Tong UniversityShanghaiChina

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