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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
Project Status Completed (Fiscal Year 2003)
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)
KeywordsDissemination / 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
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.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ei Ei Khin: "Neutral endopeptidase/CD10 expression in the stroma of epithelial ovarian carcinoma"Int J Gynecol Pathol. 22・2. 175-180 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuka Suzuki: "Possible role of placental leucine aminopeptidase in the antiproliferative effect of oxytocin in human endometrial adenocarcinoma"Clinical Cancer Research. 9・4. 1528-1534 (2003)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kazuhiko Ino: "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)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fumitaka Kikkawa: "Prognostic factors of secondary ovarian carcinoma"Oncology. 63・2. 124-129 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fuimitaka Kikkawa: "Increased Adhesion Potency of Ovarian Carcinoma Cells to Mesothelial Cells by Overexpression of Dipeptidyl Peptidase IV"International Journal of Cancer. (In press). (2002)

    • Related Report
      2002 Annual Research Report
  • [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. (In press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ei Ei Khin: "Neutral Endopeptidase/CD10 Expression in the Stroma of Epithelial Ovarian Carcinoma"International Journal of Gynecologic Pathology. (In press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahiro Suzuki: "Imbalance between Neutral Endopeptidase 24.11 and Endothelin-1 Expression in Human Endometrial Carcinoma"Oncology. 60. 258-267 (2001)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomomi Ito: "AP-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene"Biochem Biophys Res Commun. 290. 1048-1053 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Carlos Uehara: "Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells"Placenta. 22. 540-549 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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