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2003 Fiscal Year Final Research Report Summary

Interaction between ovarian carcinoma cells and mesothelial cells in peritoneal dissemination

Research Project

Project/Area Number 13671706
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNagoya University

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)

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)
Project Period (FY) 2001 – 2003
KeywordsDissemination / CD26 / ovarian carcinoma / Cadherin / Mesothelial cells
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.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Takahiro Suzuki: "Imbalance between neutral Endopeptidase 24.11 and Endothelin-1 Expression in Human Endometrial Carcinoma"Oncology. 60. 258-267 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aye Aye Thant: "Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and the PI3K-Akt pathways in ovarian cancer cells."Clin Exper Metast. 18. 423-428 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Carlos Uehara: "Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells."Placenta. 22. 540-549 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomomi Ito: "Ap-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene"Biochem Biophys Res Cdmmun. 290. 1048-1053 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroaki Kajiyama: "Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma."Cancer Research. 62・10. 2753-2757 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroaki Kajiyama: "Increased expression of dipeptidyl peptidase IV in human mesothelial cells by malignant ascites from ovarian carcinoma patients"Oncology. 63・2. 158-165 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Funtitaka Kikkawa: "Prognostic factors of secondary ovarian carcinoma."Oncology. 63・2. 124-129 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fumitaka Kikkawa: "Increased Adhesion Potency of Ovarian Carcinoma Cells to Mesothelial Cells by Overexpression of Dipeptidyl Peptidase IV"International Journal of Cancer. 105・6. 779-783 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ei Ei Khin: "Dipeptidyl Peptidase IV Expression in Endometrial Endometrioid Adenocarcinoma and Its Inverse Correlation with Tumor Grade"American Journal of Obstetrics and Gynecology. 188・3. 670-676 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ei Ei Khin: "Neutral Endopeptidase/CD10 Expression in the Stroma of Epithelial Ovarian Carcinoma."International Journal of Gynecologic Pathology. 22・2. 175-180 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroaki Kajiyama: "Dipeptidyl peptidase IV overexpression induces up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases, resulting in decreased invasive potential in ovarian carcinoma cells."Cancer Research. 63・9. 2278-2283 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhiko Irio: "Expression of placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in human normal and malignant invasive trophoblastic cells."Laboratory Investigation. 83・12. 1799-1809 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshiteru Watanabe: "Adipocyte-derived leucine aminopeptidase suppresses angiogenesis in human endometrial carcinoma via renin-angiotensin system"Clinical Cancer Research. 9・17. 6497-6503 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki T, Kikkawa F, Ino K, Nagasaka T, Tamakoshi K, Mizutani S: "Imbalance between Neutral Endopeptidase 24.11 and Endothelin-1 Expression in Human Endometrial Carcinoma"Oncology. 60. 258-267 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Thant AA, Nawa A, Kikkawa F, Ichigotani Y, Zhang Y, Sein TT, Amin R.A.R.M., Hamaguchi M: "Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and the PI3K-Akt pathways in ovarian cancer cells"Clin Exper Metast. 18. 423-428 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uehara C, Ino K, Suzuki T, Kajiyama H, Kikkawa F, Nagasaka T, Mizutani S: "Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells"Placenta. 22. 540-549 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito T, Nomura S, Okada M, Katsumata Y, Kikkawa F, Rogi T, Tsujimoto M, Mizutani S: "AP-2 and ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene, Biochem Biophys Res Commun"Biochem Biophys Res Commun. 290. 1048-1053 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kajiyama H, Kikkawa F, Suzuki T, Shibata-K, Ino K, Mizutani S: "Prolonged Survival and Decreased Invasive Activity Attributable to Dipeptidyl Peptidase IV Overexpression in Ovarian Carcinoma"Cancer Res. 62. 2753-2757 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kajiyama H, Kikkawa F, Maeda O, Suzuki T, Ino K, Mizutani S: "Increased expression of dipeptidyl peptidase IV in human mesothelial cells by malignant ascites from ovarian carcinoma patients"Oncology. 63. 158-165 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kikkawa F, Ino K, Nomura S, Ishikawa H, Kuzuya K, Yamamuro O, Kobayashi I, Kawai M, Mizutani S: "Prognostic factors of secondary ovarian carcinoma"Oncology. 63. 124-129 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kikkawa F, Kajiyama H, Ino K, Shibata K, Mizutani S: "Increased adhesion potency of ovarian carcinoma cells to mesothelial cells by overexpression of dipeptidyl peptidase IV"Int J Cancer. 105. 779-783 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Khin EE, Kikkawa F, Ino K, Kajiyama H, Suzuki T, Shibata K, Tamakoshi K, Nagasaka T, Mizutani S: "Dipeptidyl peptidase IV expression in endometrial endometrioid adenocarcinoma and its inverse correlation with tumor grade"Am J Obstet Gynecol. 188. 670-676 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Khin lEE, Kikkawa F, Ino K, Suzuki T, Shibata K, Kajiyama H, Tamakoshi K, Mizutani S: "Neutral Endopeptidase/CD10 Expression in the Stroma of Epithelial Ovarian Carcinoma"Int J Gynecol Pathol. 22. 175-180 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kajiyama H, Kikkawa F, Khin E, Shibata K, Tno K, Mizutani S: "Dipeptidyl Peptidase IV Overexpression Induces Up-Regulation of E-Cadherin and Tissue Inhibitors of Matrix Metalloproteinases, Resulting in Decreased Invasive Potential in Ovarian Carcinoma Cells"Cancer Res. 63. 2278-2283 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ino K, Kikkawa F, Suzuki T, Kajiyama H, Shibata K, Nomura S, Itakura A, Ito M, Nagasaka T, Hattori A, Tsujimoto M, Mizutani S: "Expression of placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in human normal and malignant invasive trophoblastic cells"Lab Invest. 83. 1799-1809 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe Y, Shibata K, Kikkawa F, Kajiyama H, Ino K, Hattori A, Tsujimoto M, Mizutani S: "Adipocyte-Derived Leucine Aminopeptidase Suppresses Angiogenesis in Human Endometrial Carcinoma via Renin-Angiotensin System"Clin Cancer Res. 9. 6497-6503 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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