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Study on the mechanism of extracellular matrix degradation induced by tumor cell associated fibrinolytic enzyme

Research Project

Project/Area Number 06671639
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

KOBAYASHI Takao (1995)  Hamamatsu University School of Medicine Obstetrics & Gynecology, Associate professor, 医学部, 助教授 (20107808)

茂庭 將彦 (1994)  浜松医科大学, 医学部, 助手 (00230053)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Hiroshi  Hamamatsu University School of Medicine Obstetrics & Gynecology, Research fellow, 医学部, 助手 (40178330)
TERAO Toshihiko  Hamamatsu University School of Medicine Obstetrics & Gynecology, Professor, 医学部, 教授 (60022852)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Keywordsurokinase type plasminogen activator (uPA) / plasminogen activator inhibitor (PAI) / activated Protein C (APC) / uPA / PAI-1 complex / APC / PAI-1 / PAI-2 / fibrinlysis
Research Abstract

Dissolution of and migration through basement membranes and extracellular matrices are critical steps for tumor cells. The fibrinolytic enzyme system such as urokinase type plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor, PAI) seems to play an important role in tumor invasion and metastasis formation. The uPA,which can bind uPA receptor on the surface of tumor cell membrane, can make a complex with PAI (uPA/PAI complex). The uPA/PAI complex has no fibrinolytic activity, but has only PA inhibiting activity in vitro study. But high amounts of uPA in tumor cells show poor prognosis in patients with carcinoma. This fact seems contradictory.
We proved that uPA activity of cell membrane reappear after incubation with uPA/PAI-1 complex a large amount of activated Protein C (APC) by flow cytometry and in fibrin plate assay. The uPA/PAI-1 complex was formed after 30 min incubation of 50 nM uPA and 50 nM PAI-1 at room temperature (RT), and then 30-fold molar of APC was added to the complex at RT for 30 min. The uPA/PAI-1 complex had no fibrinolytic activity, but after the incubation with APC the complex showed the fibrinolytic activity like uPA.In this study, we also proved APC could make APC/PAI-1 complex after incubation of uPA/PAI-1 complex with APC,and the activity of PAI-1 was inhibited. These facts show tumor cell associated uPA activity can be reversible even after the complex formation with PAI-1, and can degrade extracellular matrix.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Manfred Schmitt,Olaf Wilheim,Fritz Janicke,Viktor Magdolen,Ute Reuning,Hidekazu Ohi,Nobuhiko Moniwa,Hiroshi Kobayashi,Ulrich Weidle,Henner Graeff: "Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (CD87):A New Target in Tumor Invasion and Metastasis" The Journal of Obstetrics and Gynaecology. 21(2). 151-165 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nobuhiko Moniwa,Hiroshi Kobayashi,Takao Kobayashi,Toshihiko Terao: "The role of the activated protein C (APC) in fibrinolysis of human placenta." Trophoblast Research. (submitted.).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nobuhiko Moniwa,Hiroshi Kobayashi,Takao Kobayashi,Toshihiko Terao: "The relatiionship of urokinase type plasminogen activator (uPA),plasminogen activator inhibitor type-1 (PAI-1) and activated protein C (APC) in fibrinolysis of human placenta." Pollish Journal of Pharmacology. (submitted.).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Manfred Schmitt, Olaf Wilheim, Fritz Janicke, Viktor Magdolen, Ute Reuning, Hidekazu Ohi, Nobuhiko Moniwa, Hiroshi Kobayashi, Ulrich Weidle, Henner Graeff: "Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (CD87) : A New Target in Tumor Invasion and Metastasis." The Journal of Obstetrics and Gynaecology. 21 (2). 151-165 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nobuhiko Moniwa, Hiroshi Kobayashi, Takao Kobayashi, Toshihiko Terao: "The role of the activated protein C (APC) in fibrinolysis of human placenta." Trophoblast Research. (submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nobuhiko Moniwa, Hiroshi Kobayashi, Takao Kobayashi, Toshihiko Terao: "The relatiionship of urokinase type plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and activated protein C (APC) in fibrinolysis of human placenta." Pollish Journal of Pharmacology. (submitted.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 茂庭將彦: "胎盤における線維素溶解酵素の働き" 産婦人科の世界. 46. 755-760 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nobuhiko Moniwa: "The Rde of activated protein C (APC) in fibrinolysis of humam plucenta" Trophoblust Re search. (in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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