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Identification and Cloning of an inhibitor of Cancer Metastasis and Invasion

Research Project

Project/Area Number 08671882
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 (1997)  Nagoya Univ.School of Med., Lecturer, 医学部, 講師 (40224985)

玉腰 浩司 (1996)  名古屋大学, 医学部, 助手 (30262900)

Co-Investigator(Kenkyū-buntansha) NOMURA Seiji  Nagoya Univ.School of Med., Research Assistant, 医学部, 助手 (20242860)
OKAMOTO Tomomitsu  Nagoya Univ.School of Med., Research Assistant, 医学部, 助手 (70252236)
吉川 史隆  名古屋大学, 医学部, 講師 (40224985)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsOvarian Cancer / Metastasis / Fibronectin / MMP / TIMP / レチノイン酸
Research Abstract

Conditioned media of normal peritoneal, myometrial, and ovarian tissues increased MMP-2 and -9 secretion from ovarian cancer (NOM1) cells in a concentration dependent manner. Especially, MMP-9 was markedly augmented by addition of normal peritoneal tissue conditioned medium. To estimate MMP-9 stimulating factors, conditioned medium of normal peritoneal tissue was fractionated and the influence of each fraction on MMP-9 secretion was examined by zymography. More than 100 kD fraction increased mostly MMP-9 secretion from NOM1 cells. Extracellular matrix, laminine, fibronectin, and type IV collagen, were added to NOM1 cells to identify the more than 100 kD factors. Fibronectin could increase MMP-9 secretion from NOM1 cells in a concentration dependent manner. Furthermore, fibronectin induced secretion of MMP-9 was inhibited by pretreatment with RGD peptides (fibronectin receptor) and antibody against integrin alpha5 receptor. Concentration of fibronectin was 164 ng/ml after 24 hours-culture of normal peritoneal tissue. Since 100 ng/ml fibronectin was enough to stimulate MMP-9 secretion from ovarian cancer cells, fibronectin was suggested to be an important stimulating factor.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kiyosumi Shibata: "Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue." Clin.Exp.Metastasis. 15. 612-619 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyosumi Shibata: "Fibronectin Secretion from Human Peritoneal Tissue Induces Mr 92,000 Type IV Collagenase Expression and Invasion in Ovarian Cancer Cell lines." Cancer Research. 57. 5416-5420 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fumitaka Kikkawa: "Positive correlation between inhibitors of matrix metalloproteinase 1 and matrix metalloproteinase in malignant ovarian tumor tissues." Cancer Letters. 120. 109-115 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aye Aye Thant: "c-Ras is required for the activation of the matrix metalloproteinases by concanavalin A in 3Y1 cells." FEBS Letter. 406. 28-30 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koji Tamakoshi: "Hyaluronidase activity in gynaecologic cancer tissues with different metastatic forms." British Journal of Cancer. 75. 1807-1811 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoko H.Obata: "Effects of interleukin-6 on in vitro cell attachment,migration and invation of human ovarian carcinoma." Anticancer Research. 17. 337-342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyosumi Shibata, Fumitaka Kikkaw, Koji Tamakoshi, Nobuhiko Suganuma, and Yutaka Tomoda: "Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue." Clin.Exp.Metastasis. 15. 612-619 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyosumi Shibata, Fumitaka Kikkawa, Akihiro Nawa, Nobuhiko Suganuma, and Michinari Hamaguchi: "Fibronectin Secretion from Human Peritoneal Tissue Induces Mr 92,000 Type IV Collagenase Expression and Invation in Ovarian Cancer Cell Lines." Cancer Res.57. 5416-5420 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fumitaka Kikkawa, Koji Tamakoshi, Akihiro Nawa, Kiyosumi Shibata, Sadako Yamagata, Tatsuya Yamagata, Nobuhiko Suganuma: "Positive correlation between inhibitors of matrix metalloproteinase 1 and matrix metalloproteinases in malignant ovarian tumor tissues." Cancer Letters. 120. 109-115 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ay Ay Thant, Mihaela Serbulea, Fumitaka Kikkawa, Liu E.Yutaka Tomoda Yutaka, Michinari Hamaguchi: "c-Ras is required for the activation of the matrix metalloproteinases by concanavalin A in 3Y1 cells." FEBS Lett.406. 28-30 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koji Tamakoshi, Fumitaka Kikkawa, Osamu Maeda, Nobuhiko Suganuma N,Sadako Yamagata, Tatsuya Yamagata, Yutaka Tomoda: "Hyaluronidase activity in gynaecologic cancer tissues with different metastatic forms." Brit J Cancer. 75. 1807-1811 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Naoko H.Obata, Koji Tamakoshi, Kiyosumi Shibata, Fumitaka Kikkawa, Yutaka Tomoda: "Effects of interleukin-6 on in vitro cell attachment, migration and invasion of human ovarian carcinoma." Anticancer Res.17. 337-342 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kiyosumi Shibata: "Increased matrtx metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue." Clin.Exp.Metastasis. 15. 612-619 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyosumi Shibata: "Fibronectin Secretion from Human Peritoneal Tissue lnduces Mr92,000 Type IV Collagerase Expression and Invation in Ovarian Cancercell Lines." Cancer Research. 57. 5416-5420 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fumitaka Kikkawa: "Positive correlation between inhibitors of matrix metalloproteiwase I and matrix metalloproteinases in malig nant averian tumor tissues." Cancer Letters. 120. 109-115 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aye Aye Thant: "c-Ras is Required for the activation of the matrix metalloproteinases by concawavalin A in 3YI cells." FEBS Letter. 406. 28-30 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Koji Tamakoshi: "Hyaluronidaseactivity ingynecologic cancer tissues with different metastatic forms." Brit J Cancer. 75. 1807-1811 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Naoko H.Obata: "Effects of interlenkin-6 on in vitro cell attachment migration and invasion of human ovarian carcinoma" Anticancer Research. 17. 337-342 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 前田修: "婦人科悪性腫瘍における細胞外マトリックス分解酵素" Oncology and Chemotherapy. 12. 96-100 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 吉川史隆: "婦人科癌組織および細胞株におけるマトリックス分解酵素の分泌・調節機構-転移阻止へのアプローチ-:シンポジウム婦人科癌の浸潤と転移-その基礎と臨床-" 日本産婦人科学会雑誌. 48. 618-622 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Tamakoshi: "Oifferent pattern of zymography between human gyecologic normal and malignant tissues." Am.J.Obstet.Gynecol.171. 478-484 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Kato: "Suppression of gelatinase production with decreased invasiveness of choriocarcinoma cells by human recombinant interferon beta." Am.J.Obstet.Gynecol.172. 601-605 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Tamakoshi: "Characterization of extracelluler matrix-degrading proteinase and its inhibitor in gynecologic cancer tissues with clinically different matastatic forms." Cancer. 76. 2565-2571 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.H.Obata: "Effects of interleukin-6 on in vitro cell attachment,migration and invasion of human ovarian carcinoma." Anticancer Res.(1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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