New strategy of treatment for ovarian cancer aiming intraperitoneal cell-cell communication induced by microenvironmental EMT

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293341
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: Kikkawa Fumitaka 名古屋大学, 医学(系)研究科(研究院), 教授 (40224985)
• Co-Investigator(Kenkyū-buntansha): SHIBATA Kiyosumi 名古屋大学, 大学医学系研究科, 准教授 (90335026) ; KAJIYAMA Hiroaki 名古屋大学, 大学医学系研究科, 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 – 2016-03-31
• Keywords: 卵巣癌 / 腹膜播種 / 腹膜中皮細胞 / 細胞コミュニケーション / 上皮間葉転換

Outline of Final Research Achievements

The TGF-beta;-mediated alteration of the tumor microenvironment plays a crucial role in tumor progression. Mesothelial cells are the primary components of the tumor microenvironment for ovarian cancer cells (OC). We show that TGF-beta;-stimulated human primary mesothelial cells (HPMCs) 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 HPMCs by TGF-beta; stimulation, and restoration of the expression of miR-200 family members in HPMCs suppressed cancer cell attachment and proliferation. Down-regulation of the miR-200 family by TGF-beta; induced fibronectin 1 production, which promoted cancer cell attachment to HPMCs. Finally, we demonstrated that the delivery of the miR-200s to mesothelial cells in mice inhibited ovarian cancer cell implantation and dissemination.

Free Research Field

婦人科腫瘍学