2002 Fiscal Year Annual Research Report

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 Institution	Keio University
Principal Investigator	岡田保典慶應義塾大学, 医学部, 教授 (00115221)
Co-Investigator(Kenkyū-buntansha)	大西淳之北海道大学, 大学院・理学研究所, 助手 (40261276) 梁幾勇東京大学, 医科学研究所, 講師 (70332583) 佐藤博金沢大学, がん研究所, 教授 (00115239) 山本俊輔大分医科大学, 教授 (90040188) 久野耕嗣金沢大学, がん研究所, 助教授 (40242565)
Keywords	MMP / ADAM / 細胞外マトリックス代謝 / 遺伝子欠損マウス / 基質 / マトリクライン / 形態形成
Research Abstract	本特定領域研究においては、細胞外マトリックス代謝に関わるマトリックスメタロプロテアーゼ(MMP)と近縁遺伝子ファミリーのADAM分子の病的および生理的組織での作用を解析し、その生物学的意義の解明を目指している。本領域研究では(A01)「MMPの機能解析」と(A02)「ADAMの機能解析」の2つの研究項目を設定し、7名の計画研究代表者による相互の情報交換と連携により、個々の研究推進とともに共同研究を行ってきた。また、これらの研究者に加えて事務担当研究者1名と3名の評価委員の合計11名からなる総括班を構成し、研究方針の策定と研究項目の調整をしている。具体的には、ヒトがん組織における浸潤・転移関連MMP/ADAM分子の同定、発現クローニング法による酵素活性制御遺伝子探索、ジーンターゲティングによる生体内機能解析、酵母two-hybrid法による細胞膜上結合タンパクや新規基質探索などにより、MMP/ADAM分子がもつ新しい機能を細胞・組織・個体レベルで解析している。これらのうち、MT-MMPsやADAMTS1の遺伝子欠損マウスでの解析、潜在型MMP-7結合分子による細胞膜上での活性化機構、VEGFマトリクラインにおけるMMPの新規機能、MMPによる癌抑制遺伝子産物KiSS-1分子の分解などで成果をあげている。これまでの研究成果を踏まえて、「細胞-細胞外マトリックスインターフェイスプロテオリシスによる病理生理学」の新研究分野確立を目指している。

Research Products

(17 results)

All Other

All Publications (17 results)

[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)
[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)
[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)
[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)
[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)
[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)
[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)
[Publications] Enomoto H., et al.: "VEGF isoforms and their receptors are expressed in human osteoarthreitic cartilage"Am.J.Pathol.. 162. 171-181 (2003)
[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)
[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)
[Publications] Noda K., et al.: "Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy"Invest.Ophthal.Vis.Sci. (in press). (2003)
[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)
[Publications] Nakada M., et al.: "The role of matrix metalloproteinases in glioma invasion"Frontiers Bioscience. 8. E261-E269 (2003)
[Publications] Shiomi T., Okada Y.: "MT1-MMP and MMP-7 in invasion and metastasis of human cancers"Cancer Metastasis Review. (in press). (2003)
[Publications] Takino T., et al.: "Cleavage of metastasis suppressor gene product KiSS-1 protein/Metastin by matrix metalloproteinases"Oncogene. (in press). (2003)
[Publications] Takino T., et al.: "Crkl Adaptor Protein Modulates Cell Migration and Invasion in Glioblastoma"Cancer Res.. (in press). (2003)
[Publications] Nakada M., et al.: "Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases by other testican family proteins"Cancer Res.. (in press). (2003)

2002 Fiscal Year Annual Research Report

細胞外マトリックス代謝研究の新展開の総括

Principal Investigator

岡田 保典 慶應義塾大学, 医学部, 教授 (00115221)

Research Products

[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)

[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)

[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)

[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)

[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)

[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)

[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)

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

[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)

[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)

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

[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)

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

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

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

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

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

岡田保典慶應義塾大学, 医学部, 教授 (00115221)