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Regulation of adhesion molecule integrins by membrane-bound proteinase ADAM

Research Project

Project/Area Number 16390117
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionOsaka University

Principal Investigator

MATSUURA Nariaki  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (70190402)

Co-Investigator(Kenkyū-buntansha) KAWAGUCHI Naomasa  Osaka university, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70224748)
HIGASHIYAMA Shigeki  Ehime University, School of Medicine, Professor, 医学部, 教授 (60202272)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsADAM / integrin / cancer metastasis / metalloproteinase / disintegrin / )ディスインテグリン / 脳転移 / 肺癌
Research Abstract

ADAM is membrane-bound molecules composed of metalloproteinase and disintegrin. Expression of ADAM molecules of highly brain-metastatic subline and bone-metastatic subline from lung cancer cell EBC-1 cells are studied in order to clarify the implication of ADAM in cancer metastasis. As a result the expression level of ADAM9 mRNA was upregulated in brain-metastatic subline than those in bone-metastatic subline or parental cell line. Transfection of ADAM9 cDNA in kung cancer A549 cell resulted in increased NGF-stimulated invasive activity, elevated adhesion to brain tissue slices and upregulation of integrin a3b1 expression. There were no differences between transfectant and parental cell line in other integrin expression levels. When inoculated intravenously to the tail vein in skid mice, transfectants induced numerous lung and brain metastases. On the other hand parental cells or mock transfectant induced plenty of lung metastases, but not brain metastasis. These results suggested ADAM9 might play a role in brain metastasis of lung cancer.
Transfection of ADAM9 cDNA in fibrosarcoma HT1080 cell was preformed and FACS analysis of each integrin expression showed disappearance of only integrin a4 in transfectants while parental cell or mock transfectant expressed integrin a4. Decreased adhesion of transfectants to CS-1 peptide or VCAM-1 (vascular cell adhesion molecule-1), both of which are ligands of integrin a4b1, was observed. Migratory or invasive activity to CS-1 or VCAM-1 was also reduced. When inoculated intravenously to tail vein of nude mice, parent cells induced a number of lung metastases but marked decreased lung metastases were found in transfectants. There were no differences in the tumor after subcutaneous injection.
These data suggested ADAM9 might play some roles in integrin expression and also in cancer metastasis.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2007 2006 2005 2004

All Journal Article (25 results) Book (2 results)

  • [Journal Article] Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer.2007

    • Author(s)
      Ngan CY, Matsuura N, et al.
    • Journal Title

      Br J Cancer (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells.2006

    • Author(s)
      Hirao T, Matsuura N, et al.
    • Journal Title

      Exp Cell Res 312・3

      Pages: 331-339

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antisense to Cyclin D1 Inhibits Vascular Endothelial Growth Factor-Stimulated Growth of Vascular Endothelial Cells : Implication of Tumor Vascularization.2006

    • Author(s)
      Yasui M, Matsuura N, et al.
    • Journal Title

      Clin Cancer Res 12・15

      Pages: 4750-4729

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells.2006

    • Author(s)
      Hirao T, Matsuura N, et al.
    • Journal Title

      Exp Cell Res 312(3)

      Pages: 331-339

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antisense to Cyclin D1 Inhibits Vascular Endothelial Growth Factor-Stimulated Growth of Vascular Endothelial Cells : Implication of Tumor Vascularization.2006

    • Author(s)
      Yasui M, Matsuura N, et al.
    • Journal Title

      Clin Cancer Res 12(15)

      Pages: 4720-4729

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells.2006

    • Author(s)
      Hirao T, Matsuura N, et al.
    • Journal Title

      Exo Cell Res 312・3

      Pages: 331-339

    • Related Report
      2006 Annual Research Report 2005 Annual Research Report
  • [Journal Article] Aged garlic extract inhibits angiogenesis and proliferation of colorectal carcinoma cells.2006

    • Author(s)
      Matsuura N, Miyamae Y, et al.
    • Journal Title

      J Nutr 136・3

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Construction of a novel DNA decoy that inhibits the oncogenic {beta}-catenin/T-cell factor pathway.2006

    • Author(s)
      Seki Y, Matsuura N, et al.
    • Journal Title

      Mol Cancer Ther 5・4

      Pages: 985-994

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of PPARdelta in multistage carcinogenesis of the colorectum : implications of malignant cancer morphology.2006

    • Author(s)
      Takayama O, Matsuura N, et al.
    • Journal Title

      Br J Cancer 95・7

      Pages: 889-895

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Particle Irradiation Suppresses Metastatic Potential of Cancer Cells.2005

    • Author(s)
      Ogata T, Matsuura N, et al.
    • Journal Title

      Cancer Res 65・1

      Pages: 113-120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Particle Irradiation Suppresses Metastatic Potential of Cancer Cells.2005

    • Author(s)
      Ogata T, Matsuura N, et al.
    • Journal Title

      Cancer Res 65(1)

      Pages: 113-120

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Particle irradiation suppresses metastatic potential of cancer cells.2005

    • Author(s)
      Ogata T, Matsuura N, et al.
    • Journal Title

      Cancer Res 95・2

      Pages: 113-120

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of AMAP1, an ArfGAP, provides novel targets to inhibit breast cancer invasive activities.2005

    • Author(s)
      Onodera Y, Matsuura N, et al.
    • Journal Title

      EMBO J 24・5

      Pages: 963-973

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cleavage of carcinoembryonic antigen induces metastatic potential in colorectal carcinoma.2005

    • Author(s)
      Yamamoto Y, Matsuura N, et al.
    • Journal Title

      Biochem Biophys Res Commun 333・1

      Pages: 223-229

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Methylation and expression p16INK4 tumor suppressor gene in primary colorectal cancer tissues.2005

    • Author(s)
      Kim BN, Matsuura N, et al.
    • Journal Title

      Int J Oncol 26・5

      Pages: 1217-1226

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Role of p21waf1/cip1 in effects of oxaliplatin in colorectal cancer cells.2005

    • Author(s)
      Hata T, Matsuura N, et al.
    • Journal Title

      Mol Cancer Ther 4・10

      Pages: 1585-1594

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased expression of integrin alpha3betal in highly bra in metastatic subclone of a human non-small cell lung cancer cell line.2004

    • Author(s)
      Yoshimasu T, Matsuura N, et al.
    • Journal Title

      Cancer Sci 95・2

      Pages: 142-148

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of ADAM9 in Non-Small Cell Lung Cancer Correlates with Brain Metastasis.2004

    • Author(s)
      Shintani Y, Matsuura N, et al.
    • Journal Title

      Cancer Res 64・12

      Pages: 4190-4196

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] ADAM-binding protein eve-1 is required for Ectodomain shedding of EGF receptor ligands.2004

    • Author(s)
      Tanaka M, Matsuura N, et al.
    • Journal Title

      J Biol Chem 279・40

      Pages: 41950-41959

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Increased expression of integrin alpha3betal in highly brain metastatic subclone of a human non-small cell lung cancer cell line.2004

    • Author(s)
      Yoshimasu T, Matsuura N, et al.
    • Journal Title

      Cancer Sci 95(2)

      Pages: 142-148

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Overexpression of ADAM9 in Non-Small Cell Lung Cancer Correlates with Brain Metastasis.2004

    • Author(s)
      Shintani Y, Matsuura N, et al.
    • Journal Title

      Cancer Res 64(12)

      Pages: 4190-4196

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ADAM-binding protein eve-1 is required for Ectodomain shedding of EGF receptor ligands.2004

    • Author(s)
      Tanaka M, Matsuura N, et al.
    • Journal Title

      J Biol Chem 279(40)

      Pages: 41950-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Increased expression of integrin alpha3beta1 in highly brain meta-static subclone of a human non-small cell lung cancer cell line.2004

    • Author(s)
      Yoshimasu T, Matsuura N, et al.
    • Journal Title

      Cancer Sci 95・2

      Pages: 142-148

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ectodomain shedding of membrane-anchored heparin-binding EGF like growth factor and subcellular localization of the C-terminal fragment in the cell cycle.2004

    • Author(s)
      Toki F, Matsuura N, et al.
    • Journal Title

      J Cell Physiol 202・3

      Pages: 839-848

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hepatic expression of ANG2 RNA in metastatic colorectal cancer.2004

    • Author(s)
      Ogawa M, Matsuura N, et al.
    • Journal Title

      Hepatology 39・2

      Pages: 528-539

    • Related Report
      2004 Annual Research Report
  • [Book] 肝転移のすべて2005

    • Author(s)
      門田守人, 松浦成昭
    • Total Pages
      379
    • Publisher
      永井書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Book] スタンダード病理学2004

    • Author(s)
      松浦成昭, 河口直正, 他
    • Total Pages
      538
    • Publisher
      文光堂
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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