2003 Fiscal Year Final Research Report Summary
Study on novel functions of membrane-type matrix metalloproteinase in tumor metastasis
| Project/Area Number |
14370053
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
SATO Hiroshi Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (00115239)
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| Co-Investigator(Kenkyū-buntansha) |
TAKINO Takahisa Kanazawa University, Cancer Research Institute, Associate Professor, がん研究所, 助教授 (40322119)
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| Project Period (FY) |
2002 – 2003
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| Keywords | MT1-MMP / Testican / N-Tes / KiSS-1 / Mtastasis / Syndecan / Lumican / Collagen |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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