| Project/Area Number |
25670701
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nagoya University |
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Principal Investigator |
HIROAKI KAJIYAMA 名古屋大学, 医学(系)研究科(研究院), 准教授 (00345886)
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| Co-Investigator(Renkei-kenkyūsha) |
SENGA Takeshi 名古屋大学, 大学医学系研究科, 准教授 (80419431)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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 / 細胞コミュニケーション / microRNA |
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| 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.
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