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1996 Fiscal Year Final Research Report Summary

Roles of membrane-type matrix metalloproteinase in tissue organization.

Research Project

Project/Area Number 07457057
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

SEIKI Motoharu  Cancer Research Institute, Kanazawa University Professor, がん研究所, 教授 (10154634)

Co-Investigator(Kenkyū-buntansha) SATO Hiroshi  Cancer Research Institute, Kanazawa University Assistant professor, がん研究所, 助手 (00115239)
Project Period (FY) 1995 – 1996
KeywordsMatrix metalloproteinas / Membrane-type matrix metalloproteinase / Gelatinase A / TIMP-2 / Mouse embryo / Tissue remodeling
Research Abstract

Matrix metalloproteinases (MMPs) are pivotal enzymes for tissue remodeling of multicellular organisms by degrading the components of extracellular matrix. Since MMPs are secreted as inactive zymogens (pro-MMPs), they have to be activated in the tissue to function. However little is known about physiological activators in vivo where active tissue remodeling is taking place. We recently identified a membrane-type MMP (MT-MMP) as an activator of pro-MMP-2 (pro-gelatinase A=72-kDa type IV pro-collagenase) that is expressed in invasive tumors and is responsible for degradation of type IV collagen in the basement membrane. In this study we examined whether MT-MMP plays a role in activating pro-MMP-2 during mouse embryogenesis. MT-MMP expression was increased together with that of MMP-2 and its inhibitor TIMP-2 in embryos according to the days after gestation and decreased with maturation after birth.MT-MMP transcripts and the product were localized in the cells of the occificating tissues where both MMP-2 and TIMP-2 were detected. Activated MMP-2 was detected in the lysate prepared from the microdissected tissue where expression of the three genes were observed. Activated MMP-2 was propotional to the expression of MMP-2 and MT-MMP.Thus the results indicate that MMP-2 and its activator MT-MMP is a widely used system for organisms to initiate tissue remodeling on the cell surface.

Research Products

(3 results)

All Other

All Publications (3 results)

  • [Publications] 喜納 他: "MT-MMP, The cell surface activator of proMMP-2, is expressed with its substrate in mouse tissue during embryogenesis" J. Cell. Science. 109. 953-959 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 常塚 他: "Expression of MT1-MMP in tumor cells enhances pulmonary metastasis in an expervental metastasis assay" Cancer Research. 56. 5678-5683 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤 他: "MT-MMPs in tumor metastasis" J. Biochemistry. 119. 209-215 (1996)

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

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Published: 1999-03-08  

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