• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2003 Fiscal Year Final Research Report Summary

Study on novel functions of membrane-type matrix metalloproteinase in tumor metastasis

Research Project

Project/Area Number 14370053
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKanazawa University

Principal Investigator

SATO Hiroshi  Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (00115239)

Co-Investigator(Kenkyū-buntansha) TAKINO Takahisa  Kanazawa University, Cancer Research Institute, Associate Professor, がん研究所, 助教授 (40322119)
Project Period (FY) 2002 – 2003
KeywordsMT1-MMP / Testican / N-Tes / KiSS-1 / Mtastasis / Syndecan / Lumican / Collagen
Research Abstract

Membrane-type matrix metalloproteinase(MT1-MMP) is expressed on the surface of tumor cells, and thought to play an important role in tumor invasion and metastasis. However, the functions of MT1-MMP still remain unsolved, and would not be investigated by classical biochemical approach. We have developed a novel expression cloning method to screen molecules, which either regulate MT1-MMP activity or serve as substrates for it, and identified several molecules. For example, syndecan-1, expression of which is known to have reverse co-relation with the malignancy of tumors, was demonstrated to be cleaved to shed the ecto-domain. Expression of syndecan-1 was shown to suppress cell migration on collagen, which was abrogated by the cleavage of syndecan-1 by MT1-MMP. Furthermore, we identified metastasis suppressor gene product KiSS-1 protein as a substrate for MMP. Metastin peptide encoded by KiSS-1 gene was also shown to be cleaved by MMP. Metastin is known to repress cell migration by binding to the G-protein-coupled receptor(GPCR). Since metastin is inactivated by MMPs produced by tumor cells, migration of tumor cells expressing GPCR could be suppressed by co-treatment with metastin and MMP inhibitor. These results suggest that study on functions of MT1-MMP may contribute to the development of novel therapy targeting MT1-MMP.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Takino T: "Tetraspanin CD63 promotes targeting and lysosomal proteolysis of membrane-type 1 matrix metalloproteinase"Biochem Biophys Res Commun.. 304. 160-166 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takino T: "Cleavage of Metastasis Suppressor Gene Product KiSS-1 Protein/Metastin by Matrix Metalloproteinases"Oncogene. 22. 4617-4626 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakada M: "Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases by other testican family proteins"Cancer Res.. 63. 3364-3369 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takino T: "CrkI adapter protein modulates cell migration and invasion in glioblastoma."Cancer Res.. 63. 2335-2337 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Endo K: "Cleavage of Syndecan-1 by Membrane-Type Matrix Metalloproteinase-1 Stimulates Cell Migration"J.Biol.Chem.. 278. 40764-40770 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takino T: "Membrane-Type 1 Matrix Metalloproteinase Regulates Collagen-dependent Mitogen-Activated Protein/Extracellular Signal-Related Kinase Activation and Cell Migration"Cancer Res.. 印刷中. (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤 博: "癌転移"日本臨床. 4 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takino T, Miyamori H, Kawaguchi N, Uekita T, Seiki M. Sato H.: "Tetraspanin CD63 promotes targeting and lysosomal proteolysis of membrane-type 1 matnx metalloproteinase."Biochem Biophys Res Commun.. 304. 160-166 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takino, T., Koshikawa, N., Miyamori, H., Tanaka, M., Sasaki, T., Okada, Y., Seiki, M., Sato.H.: "Cleavage of Metastasis Suppressor Gene Product KiSS-1 Protein/Metastin by Matrix Metalloproteinases."Oncogene. 22. 4617-4626 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takino T, Nakada M, Miyamori H, Yamashita J, Yamada KM, Sato H.: "CrkI adapter protein modulates cell migration and invasion in glioblastoma."Cancer Res.. 63. 2335-2337 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakada, M., Miyamori, H., Yamashita, J, Sato, H.: "Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases by other testican family proteins."Cancer Res.. 63. 3364-3369 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Endo K., Takino, T., Miyamori, H., Kinsen, H., Yoshizaki, T., Furukawa, M., Sato, H.: "Cleavage of Syndecan-1 by Membrane-Type Matrix Metalloproteinase-1 Stimulates Cell Migration."J.Biol.Chem.. 278. 40764-40770 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takino, T., Miyamori, H., Watanabe, Y., Yoshioka, K., Sato, H.: "Membrane-Type 1 Matrix Metalloproteinase Regulates Collagen-dependent Mitogen-Activated Protein/Extracellular Signal-Related Kinase Activation and Cell Migration."Cancer Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2005-04-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi