New direction for the conquest of the EMT-related peritoneum dissemination in chemoresistant ovarian cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670701
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: HIROAKI KAJIYAMA 名古屋大学, 医学(系)研究科(研究院), 准教授 (00345886)
• Co-Investigator(Renkei-kenkyūsha): SENGA Takeshi 名古屋大学, 大学医学系研究科, 准教授 (80419431)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 卵巣癌 / 腹膜播種 / マイクロRNA / TGF-β / 腹膜中皮細胞 / 薬剤耐性 / 腹腔内微小環境

Outline of Final Research Achievements

Mesothelial cells (MC) are the primary components of the tumor microenvironment for ovarian cancer (OC) cells. We show that TGF-beta-stimulated human MC (Cancer-associated mesothelial cells: CAM) are able to promote cancer cell attachment and proliferation and the activation of the promoter activities of MMP-2 and MMP-9, which are metalloproteinases necessary for tumor invasion. Expression of the miR-200 family was down-regulated in CAM, and restoration of the expression of miR-200 family members in MC suppressed cancer cell attachment and proliferation. Down-regulation of the miR-200 family by TGF-beta-induced Fibronectin production, which promoted cancer cell attachment to CAM. Finally, we demonstrated that the delivery of the miR-200s to CAM in mice inhibited OC cell implantation and dissemination. Our results suggest that alteration of the tumor microenvironment by the miR-200 family could be a novel therapeutic strategy for OC treatment.

Free Research Field

婦人科腫瘍学