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細胞外マトリックス代謝研究の新展開の総括

Research Project

Project/Area Number 11240101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKeio University

Principal Investigator

岡田 保典  慶應義塾大学, 医学部, 教授 (00115221)

Co-Investigator(Kenkyū-buntansha) 佐藤 博  金沢大学, がん研究所, 教授 (00115239)
梁 幾勇  東京大学, 医科学研究所, 講師 (70332583)
大西 淳之  北海道大学, 大学院・理学研究科, 助手 (40261276)
久野 耕嗣  金沢大学, がん研究所, 助教授 (40242565)
山本 俊輔  別府大学, 栄養学科, 教授 (90040188)
岡田 明子  東京大学, 医科学研究所, 助手 (00233320)
Project Period (FY) 1999 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2002: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2001: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2000: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1999: ¥300,000 (Direct Cost: ¥300,000)
Keywords酵素 / 細胞・組織 / 細胞外マトリックス / MMP / ADAM / 癌細胞浸潤・転移 / 細胞外マトリックス代謝 / 増殖因子 / 浸潤・転移 / 基質 / 形態形成 / 遺伝子欠損マウス / マトリクライン / クローニング
Research Abstract

特定領域研究「細胞外マトリックス代謝研究の新展開」においては、細胞外マトリックスの代謝に関わるマトリックスメタロプロテアーゼ(Matrix metalloproteinase=MMP)と近縁のADAM (A disintegrin and metalloproteinase)両遺伝子ファミリーの病的および生理的組織での作用を細胞外マトリックス代謝の観点から解析し、MMP/ADAM分子の生物学的意義と新規機能を細胞・組織および個体レベルで解明することを研究目標として、「MMPの機能解析」と「ADAMの機能解析」の研究項目に属する計画研究代表者がそれぞれの研究課題でMMP/ADAM分子の新規機能を明らかにするとともに個々の研究成果を相互に比較・検討することで、両者の生物学的意義を明らかにしてきた。これらの研究成果については、最終結果としてA(期待どおりの研究が進展した)の評価を得た。
これらの研究成果を取りまとめて、広く社会に還元して行くことは極めて意義のある重要なことであることから、本研究課題では、(1)本特定領域研究の各計画研究代表者による公開シンポジウムを平成16年8月31日に開催するとともに、(2)各計画研究代表者の平成11年度〜15年度の研究成果の総括と、発表論文、特許、などのリストに主な発表論文の別冊を加えて研究成果報告書の作成を行い、報告書を全国の各研究・教育施設へ配布する。

Report

(6 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Endo K., Sato H., et al.(7番目/7名): "Cleavage of syndecan-1 by membrane-type matrix metalloproteinase-1 stimulates cell migration."J.Biol.Chem.. 278. 40764-40770 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Enomoto H., Okada Y., et al.(9番目/9名): "VEGF isoforms and their receptors are expressed in human osteoarthritic cartilage."Am.J.Pathol.. 162. 171-181 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takino T., Okada Y., et al.(6番目/8名): "Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by MMPs."Oncogene. 22. 4617-4626 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuda A, Yana I, (5番目/6名): "Clusterin, an abundant serum factor, is a possible negative regulator of MT6-MMP/MMP-25 produced by neutrophils."J Biol Chem.. 278. 36350-36357 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okada Y.: "Proteinases and matrix degradation. In Kelley's Textbook of Rheumatology. 7th edition(Ed.by Harris E.D., Jr., et al.)"W.B.Saunders Philadelphia (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inoki I., et al.: "Connective tissue growth factor binds Vascular endothelial growth factor (VEGF) and inhibits VEGA-induced angiogenesis"FASEB. J16. 219-221 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aoki T., et al.: "Two-step sandwich enzyme immunoassay using monoclonal antibodies for detection of soluble and membrane-associated human membrane type 1-matrix metalloproteinase"J.Immunoassay Immunochem.. 23. 49-68 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashimoto G., et al.: "Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165"J.Biol.Chem.. 277. 36288-36295 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maekawa K, et al.: "Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model"Clin.Exp.metastasis. 19. 513-518 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamura T., et al.: "Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in nonsmall cell lung carcinomas"Lung Cancer. 35. 249-255 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori H., et al.: "CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain"EMBO J.. 21. 3949-3959 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takino T., et al.: "A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine-phosphorylated"Oncogene. 21. 6488-6497 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto H., et al.: "VEGF isoforms and their receptors are expressed in human osteoarthreitic cartilage"Am.J.Pathol.. 162. 171-181 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiomi T., et al.: "Empysematous are caused by degradition of type III collagen in transgenic mice expressing MMP-1"Exp.Lung Res.. 29. 1-15 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Pucci-Minafra I., et al.: "Qualitative analysis of circulating and forms of gelatinase A(MMP-2) and B(MMP-9) in colon carcinomas by mono-and two-dimensional gelatin zymography"Matrix Biol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noda K., et al.: "Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy"Invest.Ophthal.Vis.Sci. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Foronjy R.F., et al.: "Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung"Am.J.Physiol.Lung Cell Mole.Biol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakada M., et al.: "The role of matrix metalloproteinases in glioma invasion"Frontiers Bioscience. 8. E261-E269 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiomi T., Okada Y.: "MT1-MMP and MMP-7 in invasion and metastasis of human cancers"Cancer Metastasis Review. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takino T., et al.: "Cleavage of metastasis suppressor gene product KiSS-1 protein/Metastin by matrix metalloproteinases"Oncogene. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takino T., et al.: "Crkl Adaptor Protein Modulates Cell Migration and Invasion in Glioblastoma"Cancer Res.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakada M., et al.: "Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases by other testican family proteins"Cancer Res.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Misumi Y. et al.: "An essential cytoplasmic domain for the Golgi localization of Coiled-coil proteins with a COOH-terminal membrane anchor"J.Biol.Chem.. 276. 6867-6873 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyamori H. et al.: "Claudin promotes activation of pro-MMP-2 mediated by membrane-type matrix metalloproteinases"J.Biol.Chem.. 276. 28204-28211 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itoh Y. et al.: "Dimer formation of MT1-MMP is essential for proMMP-2 activation and promoting tumor cell invasion"EMBO J.. 20. 4782-4793 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kita D. et al.: "Expression of dominant negative form of Ets-1 suppresses fibronectin-stimulated cell adhesion and migration through down-regulation of integrin a5 expression in U251 glioma cell line"Cancer Res.. 61. 7985-7991 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakada M. et al.: "Suppression of MT1-MMP-mediated MMP-2 activation and tumor invasion by testican 3 and its splicing variant gene product N-Tes"Cancer Res.. 61. 8889-8902 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakada M. et al.: "Roles of membrane-type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant gliomas"J Neurosurg.. 94. 464-473 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoki I. et al.: "Connective tissue growth factor binds vascular endothelial growth factor(VEGF) and inhibits VEGF-induced angiogenesis"FASEB J. 16. 219-221 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okada Y.: "Kelley's Textbook of Rheumatology."W.B.Saunders Company.. 55-72 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shido T., et al.:: "ADAMTS-1: a metalloproteinasde-disintegrin essential for growth, fertility, and organ morphology and function."J.Clin.Invest.. 105. 1345-1352 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura H., et al.:: "Brevican is degraded by matrix metalloproteinases (MMPs) and aggrecanase-1 (ADAMTS4) at the different sites. J. Biol. Chem."J.Biol.Chem.. 275. 38885-38890, (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamanaka H. et al.:: "Expression and tissue localization of membrane-types 1,2 and 3 matrix metalloproteinases in rheumatoid arthritis."Lab.Invest.. 80. 677-687, (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takizawa M. et al.:: "Production of tissue inhibitor of metalloproteinases-3 is selectively enhanced by calcium pentosan polysulfate in human rheumatoid synovial fibroblasts."Arthritis Rheum.. 43. 812-820, (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kuno K. et al.:: "ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan."FEBS Lett. 478. 241-245 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murono S. et al.:: "Aspirin inhibits tumor cell invasiveness induced by Epstein-Barr virus latent membrane protein 1 through suppression of matrix metalloproteinase-9 expression."Cancer Res.. 60. 2555-2561 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakada M.: "Expression and tissue localization of membrane-types 1, 2, 3 matrix metalloproteinases in human astrocytic tumors"Am. J. Pathol.. 154. 417-428 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura H.: "Enhanced production and activation of progelatinase A mediate by membrane-type 1 matrix metalloproteinase in human papillary thyroid carcinomas"Cancer Res.. 59. 467-473 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimada T.: "Characterization of a truncated recombinant form of human membrane type 3 matrix metalloproteinase"Eur. J. Biochem.. 262. 907-914 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda M.: "Expression of vascular endothelial growth factor isoforms and their teceptors Flt-1, KDR and neuropilin-1 in synovial tissues of rheumatoid arthritis"J Pathol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamanaka H.: "Expression and tissue localization of membrane-types 1, 2 and 3 matrix metalloproteinases in rheumatoid arthritis"Lab. Invest.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishida S.: "Co-expression of VEGF receptors VEGF-R2 and neuropilin-1 in proliferative diabetic retinopathy"Invest. Ophthalmol. Vis. Sci.. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2018-03-28  

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