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Structure and Function of Laminin-5, a Cell Adhesion Protein of Basement Membrane

Research Project

Project/Area Number 11490030
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 広領域
Research InstitutionYokohama City University

Principal Investigator

MIYAZAKI Kaoru  Yokohama City University, Kihara Institute for Biological Research, Professor, 木原生物学研究所, 教授 (70112068)

Co-Investigator(Kenkyū-buntansha) HIGASHI Shouichi  Yokohama City University, Kihara Institute for Biological Research, Research Associate, 木原生物学研究所, 助手 (10275076)
YASUMITSU Hidetaro  Yokohama City University, Kihara Institute for Biological Research, Associate Professor, 木原生物学研究所, 助教授 (10182346)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordslaminin-4 / cell adhesion / cell motility / globular domain / processing / MT-MMP / tumor invasion / basement membrane
Research Abstract

The basement protein laminin-5(LN5), a heterotrimer of laminin α3, β3 and γ2 chains, potently promotes cellular adhesion and motility. In this study, we investigated the structure and function relationship of LN5 and its pathological roles in tumor invasion. 1) The α3 chain of LN5 contains five globular domains (G1 to G5) in its carboxyl end. To clarify the function of each G domain, we transfected cDNAs for the full length and five deletion derivatives of the α3 chain into human HT1080 cells, which express only the laminin β3 andγ2 chains, and prepared recombinant LN5s lacking each G domain. The deletion of G5 or G4-5 did not affect the biological activities of LN5, but the LN5 without G3-5 showed little activities of cell adhesion and migration. It was also found that G3 contained two different regions to stimulate cell adhesion and migration. Furthermore, we found that the α3 chain was cleaved between G3 and G4 after secretion and determined the cleavage site. 2) The 105-kDa γ2 chain of LN5 is cleaved at an amino-terminal region to produce the 105-kDa form. We found that MT1-MMP catalyzed this processing, and that this processing increased the cell motility activity of LN5 but decreased its cell adhesion activity. These results demonstrate that the amino-terminal region of γ2 chain has an important effect on the biological activity of LN5. 3) Immunohistochemical analysis showed that the laminin γ2 chain monomer was overexpressed in invading human carcinoma cells. When a cDNA for the amino-terminal regions of the γ2 chain was transfected into a human carcinoma cell line, the invasive potential of this cell line in vivo was greatly enhanced. These results suggest that the γ2 chain itself plays some important roles in tumor invasion.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Kagesato, Y., Miyazaki, K.et al.: "Sole expression of laminin g2 chain in invading tumor cells and its assoication with stromal fibrosis in lung adenocarcinomas"Jpn. J. Cancer Res.. 92. 184-192 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Adachi, Y., Miyazaki, K.et al.: "Expression at anglomodulln (TAP/Mac 25) in invading tumor cells and blood vessels correlates with tumor progression and poor prognosis in human colorecral cancers"Int. Cancer Res.. 95. 216-222 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jin, M., Miyazaki, K.et al.: "Expression of serine proteinase inhibitor PP5/TFPI-2/MSPI decreases invasive potential of human choriocarcinoma cells in vitro and in vivo"Gynecol. Oncol.. 83. 325-333 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishikwa, I., Miyazaki, K.et al.: "Matrilysin stimulates DNA synthesis of cultured vascular endothellal cells and induces angiogenesis in vivo"Cancer Lett.. 173. 175-182 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Huo, H., Miyazaki, K.et al.: "MMP-7 (matrilysin) accelerated growth of human umbilical vein enclothelial cells (HUVECs)"Cancer Lett.. 177. 95-100 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mizushima, H., Miyazaki, K.et al.: "Expression of laminin-5 enhances turnorigenicity of human fibrosarcoma cells in nude mice"Jpn. J. Cancer Res.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 宮崎香, 森山佳谷乃: "バイオサイエンスの新世紀。第8巻:多細胞体の構築と細胞接着システム(関口清俊, 鈴木信太郎編)"共立出版(分担). 174-186 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kagesato, Y., Miyazaki, K.et al.: "Sole expression of laminin g2 chain in invading tumor cells and its assoication with stromal fibrosis in lung adenocarcinomas"Jpn. J. Cancer Res.. 92. 184-192 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Adachi, Y., Miyazaki, K.et al.: "Expression of angiomodulin (TAF/Mac 25) in invading tumor cells and blood vessels correlates with tumor progression and poor prognosis in human colorectal cancers"Int. Cancer Res.. 95. 216-222 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jin, M., Miyazaki, K.et al.: "Expression of serine proteinase inhibitor PP5/TFPI-2/MSPI decreases invasive potential of human choriocarcinoma cells in vitro and in vivo"Gynecol. Oncol.. 83. 325-333 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishikwa, I., Miyazaki, K.et al.: "Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo"Cancer Lett.. 173. 175-182 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Huo, H., Miyazaki, K.et al.: "MMP-7 (matrilysin) accelerated growth of human umbilical vein endothelial cells (HUVECs)"Cancer Lett.. 177. 95-100 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mizushima, H., Miyazaki, K.et al.: "Expression of laminin-5 enhances tumorigenicity of human fibrosarcoma cells in nude mice"Jpn. J Cancer Res.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 宮崎香, 森山佳谷乃: "バイオサイエンスの新世紀。第8巻:多細胞体の構築と細胞接着システム(関口清俊, 鈴木信太郎 編)"共立出版(分担). 174-186 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kishibe,J.Miyazaki,K. et al.: "Structural Requirements of Heparan Sulfate for the Binding to the Tumor-derived Adhesion Factor/Angiomodulin That Induces Cord-like Structures to EVC-304 Human Carcinoma Cells."J.Biol.Chem.. 275. 15321-15329 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ebihara,N.Miyazaki,K. et al.: "The functions of exogenous and endogenous laminin-5 on corneal epithelial cells."Exp.Eye Res.. 71. 69-79 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirosaki,T.Miyazaki,K. et al.: "Structural requirement of carboxyl-terminal globular domains of laminin α3 chain for promotion of repid cell adhesion and migration by laminin-5."J.Biol.Chem. 275. 22495-22502 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe,K.Miyazaki,K. et al.: "Interaction with heparin and matrix metalloproteinase-2 cleavage expose a cryptic anti-adhesive site fibronectin."Biochemsitry. 39. 7138-7144 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsubota,Y.Miyazaki,K. et al.: "Isolation and activity of proteolytic fragent of laminin-5 α3 chain5."Biochem.Biophys.Res.Commun. 278. 614-620 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kagesato,Y.Miyazaki,K. et al.: "Sole expression of laminin g2 chain in invading tumor cells and its association with stromal fibrosis in lung adenocarcinomas."Jpn.J.Cancer Res.. 92. 184-192 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koshikawa,N.,Miyazaki,K.et al.: "Overexpression of laminin γ2 chain monmer in invading gastric carcinoma cells."Cancer Res.. 59. 5596-5601 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyata,KS.,Miyazaki,K.et al.: "Trypsin stimulats integrin α5β1-dependent adhesion to fibronectin and proliferation of human gastric varcinoma cells through activation of proteinase-activated receptor-2."J.Biol.Chem.. 275. 4592-4598 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koshikawa,N.,Miyazaki,K.et al.: "Role of cell surface metalloproteinase MT1-MMP in epithelial cell migration over laminin-5."J.Cell Biol.. 148. 615-624 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kishibe,J.Miyazaki,K.et al.: "Structural requirements of heparan sulfate for the specific bunding to angiomodulin (TAF/Mac25) that induces morphological changesof human carcinoma cells expressing syndecan-1 and -4."J.Biol.Chem.. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ebihara,N.,Miyazaki,K.et al.: "The functions of exogenous and endogenous laminin-5 on corneal epithelial cells."Exp.Eye Res.. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirosaki,T.,Miyazaki,K.et al.: "Structural requirement of carboxyl-terminal globular domains of laminin α3 chain for promotion of rapid cell adhesion and migration by laminin-5."J.Biol.Chem.. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 岡田雅人、宮崎香(編著): "改訂タンパク質実験ノート(上下巻)"羊土社.

    • Related Report
      1999 Annual Research Report

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Published: 2000-04-01   Modified: 2018-07-04  

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