| Project/Area Number |
13671706
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (40224985)
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| Co-Investigator(Kenkyū-buntansha) |
KAJIYAMA Hiroaki Nagoya University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (00345886)
SHIBATA Kiyosumi Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (90335026)
INO Kazuhiko Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (60303640)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Dissemination / CD26 / ovarian carcinoma / Cadherin / Mesothelial cells / 接着 / ファイブロネクチン / アミノペプチダーゼ |
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| Research Abstract |
1.The expression of dipeptidyl peptidase IV (CD26) was confirmed in endometrial cancer tissues by immunohistochemical staining. The staining intensity decreased according to undifferentiation.
2.The DPPIV cDNA was transfected into ovarian cancer cells (SKOV3). Growth rate did not changed in transfected cells (SKDPIV) compared to SKOV3 or vector transfected cells (SKpcDNA). However, migration and invasion potential significantly decreased in SKDPIV cells. Adhesion rate to mesothelial cells was significantly enhanced in SKDPIV cells, but not in SKpcDNA cells. Furthermore, DPPIV transfection induced morphological change from spindle to cobblestone like shape, while morphology of SKpcDNA cells were same as SKOV3 cells with spindle shape morphology.
3.IL-1b, TNFa, and VEGE, which are much in malignant ascites, could increase DPPIV expression in mesothelial cells in a dose-dependent manner, while TGFb1 reduced expression of DPPIV.
4.Transfection of DPPIV into SKOV3 cells enhanced E-cadherin and b-catenin expression. Furthermore, increased MMP-2 and MT1-MMP were observed in SKDPIV cells, while TLMIP-1 and -2 were decreased.
5.We inoculated these 3 types of cells into nude mice. 30 days after inoculation, a number of disseminated tumors were observed in nude mice inoculated with SKOV3 or SKpcDNA cells, but no clear dissemination was observed in nude mice inoculated with SKPCDNA cells. Finally, prolonged survival was observed in nude mice inoculated with SKDPIV cells.
6.Stromal derived factor 1a (SDF-1a), one of the DPPIV substrates, could increase progression and invasion in SKOV3 cells, but not in SKDPIV cells.
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