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2014 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number 25670701
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionNagoya 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

URL: 

Published: 2016-06-03  

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