| Project/Area Number |
25293341
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nagoya University |
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Principal Investigator |
Kikkawa Fumitaka 名古屋大学, 医学(系)研究科(研究院), 教授 (40224985)
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| 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)
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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 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| 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 / 癌関連中皮細胞 / 中皮細胞 / TGF-ベータ / 転移・浸潤 |
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| 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.
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