| Project/Area Number |
08044262
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research . |
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| Research Field |
Experimental pathology
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| Research Institution | School of Medicine, Keio University (1997)
Kanazawa University (1996) |
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Principal Investigator |
OKADA Yasunori Keio University, School of Medicine, Pathology, Professor, 医学部, 教授 (00115221)
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| Co-Investigator(Kenkyū-buntansha) |
D'ARMIENTO J コロンビア大学, 医学部・内科学, 助教授
SHIKATA Hideo School of Dentistry, Meikai University, Pathology, Research Associte, 歯学部・口腔病理, 助手 (00170853)
OHNO Shinsuke Cancer Research Institute, Kanazawa University, Professor, がん研究所・腫瘍制御, 教授 (70019868)
SHIOZAWA Shuninchi Kobe University, School of Medicine, Professor, 医学部・保健学科, 教授 (40154166)
CHADA Kiran UMDNJ-RWJ Medical School, Biochemistry, Associate Professor, 生化学, 助教授
ARMIENTO Jeanine D Columbia University, School of Medicine, Associate Professor
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| Project Period (FY) |
1996 – 1997
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| Keywords | ECM degradation / Transgenic mice / Matrix metalloproteinase / Tissue destruction / Cancer invasion / Metastasis |
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| Research Abstract |
Among the matrix metalloproteinase (MMP) gene family members, MMP-2 (gelatinase A) is believed to be involved in cancer invasion and metastasis and joint destruction, and thus its function in vivo is important. Membrane-type MMPs (MT-MMPs) were recently cloned as acribators of proMMP-2 and the degradation mechanism of extracellular matrix by the MT-MMPs/MMP-2 system is one of the key projects in the field of MMP research. In the present studies, we have demonstrated that proMMP-2 activation is mediated by MT1-MMP in the human invasive breast carcinomas and human thyroid carcinomas. In the human osteoarthritic and rheumatoid arhtritic cartilages, MT1-MMP also playd a major role in the activation of proMMP-2, showing a positive correlation with cartilage destruction. We also revealed that MT1-MMP is an extracellular matrix-degrading proteinase capable of digesting interstitial collagens and aggrecan as well as an activator of proMMP-2. MT3-MMP had a similar acitivity against these substrates except for type I collagen. Transgenic mice expressing MT1-MMP specifically in the cartilages are being made and analyzes of their phenotypes are now under way. These mice will be back crossed with MMP-2 knockout mice which had been made by a Japanese group and their phenotypes will be examined.
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