Study on mechanism of tissue degradation by membrane-type matrix metalloproteinase

• Project/Area Number: 19390084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kanazawa University
• Principal Investigator: SATO Hiroshi Kanazawa University, がん研究所, 教授 (00115239)
• Co-Investigator(Kenkyū-buntansha): TAKINO Takahisa 金沢大学, がん研究所, 准教授 (40322119)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2008: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2007: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
• Keywords: MT1-MMP / 組織破壊 / MMP-2 / GDF-15 / 細胞接着斑 / ERK / 細胞運動 / 分子標的 / GDF15 / TIMP-2 / 活性化 / p53 / p21

Research Abstract

膜型マトリックスメタロプロテアーゼー1(MT1-MMP)の機能は、潜在型MMP-2の活性化と基質切断の2つに大別できる。人工的MMP-2受容体MSP-TIMP-2を考案してMMP-2活性化機構の解明とMMP-2活性化の生理的意義を明らかにした。また、MT1-MMP新規基質を同定し、がん浸潤・転移に果たす役割を解明した。さらにMT1-MMPの細胞接着斑における機能を解析し、細胞運動なに果たす役割を解明した。

Research Products

• [Journal Article] Cyclooxygenase-2 is involved in the up-regulation of matrix metalloproteinase-9 in cholangiocarcinoma induced by tumor necrosis factor-alpha (2009)
  • Author(s): Itatsu K, Sasaki M, Yamaguchi J, Ohira S, Ishikawa A, Ikeda H, Sato Y, Harada K, Zen Y, Sato H, Ohta T, Nagino M, Nimura Y, Nakanuma Y.
  • Journal Title: Am. J. Pathol 174 Pages: 829-841
• [Journal Article] Cyclooxygenase-2 is involved in the up-regulation of matrix metalloproteinase-9 in cholangiocarcinoma induced by tumor necrosis factor-alpha (2009)
  • Author(s): Itatsu K
  • Journal Title: Am. J. Pathol. 174 Pages: 829-841
  • Peer Reviewed
• [Journal Article] The scaffold protein c-Jun NH2-terminal kinase-associated leucine zipper protein regulates cell migration through interaction with the G protein Gα13 (2008)
  • Author(s): Gantulga D, Baljinnyam Tuvshintugs B, Endo Y, Takino T, Sato H, Murakami S, Yoshioka K.
  • Journal Title: J. Biochemistry 114 Pages: 693-700
• [Journal Article] Activation of Matrix Metalloproteinase (MMP)-2 By Membrane-type 1-MMP Through An Artificial Receptor For ProMMP-2 Generates Active MMP-2 (2008)
  • Author(s): Nishida Y, Miyamori H, Thompson E.W, Takino T., Endo Y., Sato H.
  • Journal Title: Cancer Res. 68 Pages: 9096-9104
• [Journal Article] Phosphorylation of extracellular signal-regulated kinase 1/2, p^<38> mitogen-activated protein kinase and nuclear translocation of nuclear factor-kappaB are involved in upregulation of matrix metalloproteinase-9 by tumour necrosis factor-alpha (2008)
  • Author(s): Itatsu K, Sasaki M, Harada K, Yamaguchi J, Ikeda H, Sato Y, Ohta T, Sato H, Nagino M, Nimura Y, Nakanuma Y.
  • Journal Title: Liver Int. 29 Pages: 291-298
• [Journal Article] Arsenic enhances matrix metalloproteinase-14 expression in fibroblasts (2008)
  • Author(s): Kato M., Hossain K, Iida M, Sato H, Uemura N, Goto Y.
  • Journal Title: Toxicol Environ Health A 71 Pages: 1053-1055
• [Journal Article] Phosphorylation of extracellular signal-regulated kinase1/2, p38 mitogen-activated kinase and nuclear translocation of nuclear factor-kappaB are involved in upregulation of matrix metalloproteinase-9 by tumor necrosis factor-alpha. (2008)
  • Author(s): Itatsu K
  • Journal Title: Liver Int. 29 Pages: 291-298
  • Peer Reviewed
• [Journal Article] Arsenic enhances matrix metalloproteinase-14 expression in fibroblasts. (2008)
  • Author(s): Kato M
  • Journal Title: J. Toxicol. Environ. Health 71 Pages: 1053-1055
  • Peer Reviewed
• [Journal Article] The scaffold protein c-Jun NH2-terminal kinase-associated leucine zipper protein regulates cell migration through interaction with the G protein Gal3. (2008)
  • Author(s): Gantulga D
  • Journal Title: J. Biochemistry 144 Pages: 693-7000
  • Peer Reviewed
• [Journal Article] Activation of Matrix Metalloproteinase (MMP)-2 By Membrane-type 1-MMP Through An Artificial Receptor For Pro MMP-2 Generates Active MMP-2. (2008)
  • Author(s): Nishida Y
  • Journal Title: Cancer Research 68 Pages: 9096-9014
  • Peer Reviewed
• [Journal Article] Inhibition of Membrane-Type Matrix Metalloproteinase at Cell-Matrix Adhesions (2007)
  • Author(s): Takino T., Saeki H., Miyamori H., Kudo T., Sato H.
  • Journal Title: Cancer Res 67 Pages: 11621-11629
• [Journal Article] Cleavage of growth differentiation factor 15 (GDF15) by membrane type 1-matrix metalloproteinase abrogates GDF15-mediated suppression of tumor cell growth (2007)
  • Author(s): Abd El-Aziz SH., Endo Y., Miyamaori H., Takino T., Sato H.
  • Journal Title: Cancer Sci 98 Pages: 1330-1335
  • NAID: 10019998291
• [Journal Article] Crosstalk between neovessels and mural cells directs the site- specific expression of MT1-MMP to endothelial tip cells (2007)
  • Author(s): Yana, I., Sagara H., Takaki S., Takatsu K., Nakamura K., Nakao K., Katsuki M., Taniguchi S., Aoki T., Sato H., Weiss S.J., Seiki M.
  • Journal Title: J. Cell Sci. 120 Pages: 1607-1614
• [Journal Article] Regulation of N-cadherin-based cell-cell interaction by JSAP1 scaffold in PC12h cells (2007)
  • Author(s): Bayarsaikhan B., Takino T., Gantulga D., Sato H., Ito T. Yoshioka K
  • Journal Title: Biochem.Biophys.Res.Commum 353 Pages: 357-362
  • NAID: 120000809366
• [Journal Article] Substrate choice of membrane-type matrix metalloproteinase-1 is dictated by tissue inhibitor of matrix metalloproteinase-2 levels. (2007)
  • Author(s): Kudo T., Takino T., Miyamori H., Thompson E.W., Sato H.
  • Journal Title: Cancer Sci. 98 Pages: 563-568
• [Journal Article] Inhibition of Membrane-Type Matrix Metalloproteinase at Cell-Matrix Adhesions. (2007)
  • Author(s): Takahisa Takino
  • Journal Title: Cancer Research 67 Pages: 11621-11629
  • Peer Reviewed
• [Journal Article] Cleavage of growth differentiation factor 15 (GDF 15) by membrane type 1-matrix metalloproteinase abrogates GDF 15-mediated suppression of tumor cell growth. (2007)
  • Author(s): El-Aziz Abd
  • Journal Title: Cancer Science 98 Pages: 1330-1335
  • Peer Reviewed
• [Journal Article] Substrate cnolce of membrane-type matrix metalloprotelnase-1 is dictated by tissue inhibitor of matrix metalloproteinase-2 levels. (2007)
  • Author(s): Tomoya Kudo
  • Journal Title: Cancer Science 98 Pages: 563-568
  • Peer Reviewed
• [Journal Article] Oncogenic role of Epstein-Barr virus-encoded small RNAs (EBERs) in nasopharyngeal carcinoma. (2007)
  • Author(s): Tomokazu Yoshizaki
  • Journal Title: Auris Nasus Larynx 34 Pages: 73-78
  • Peer Reviewed
• [Journal Article] Crosstalk between neovessels and mural cells directs the site-specific expression of MT1-MMP to endothelial tip cells (2007)
  • Author(s): Ikuo Yana
  • Journal Title: J Cell Science 120 Pages: 1607-1614
  • Peer Reviewed
• [Journal Article] N-cadherin- based cell-cell interactlon by JSAP1 scaffold in PC12h cells. (2007)
  • Author(s): Munkhuu Bayarsaikhan
  • Journal Title: Biochem. Biophys. Res. Commun. 353 Pages: 357-362
  • Peer Reviewed
• [Presentation] MT1-MMP活性制御機構の解析シンポジウム (2008)
  • Author(s): 佐藤博、滝野隆久
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] MT1-MMPはFAKとERKを介して細胞増殖と浸潤を増強する (2008)
  • Author(s): 滝野隆久、佐藤博
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-29
• [Presentation] MT1-MMPはERKを介して細胞増殖と浸潤を増強する (2008)
  • Author(s): 滝野隆久, 佐藤博
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] MT1-MMPによる細胞外マトリックス再構築誘導 (2008)
  • Author(s): 小澤晃正、滝野隆久、西田有希、佐藤博
  • Organizer: 第17回日本がん転移学会
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-07-25
• [Presentation] MT1-MMPによるMMP-2活性化は転移を増強する(優秀演題賞) (2008)
  • Author(s): 西田有希、滝野隆久、佐藤博
  • Organizer: 第17回日本がん転移学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-07-24
• [Presentation] MT1-MMPによる浸潤性増殖誘導 (2008)
  • Author(s): 滝野隆久、小澤晃正、西田有希、佐藤博
  • Organizer: 第17回日本がん転移学会
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-07-24
• [Presentation] MT1-MMPによるMMP-2活性化は転移を増強する (2008)
  • Author(s): 西田有希, 佐藤博
  • Organizer: 日本がん転移学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-07-24
• [Presentation] MT1-MMPによる浸潤性増殖誘導 (2008)
  • Author(s): 滝野隆久, 佐藤博
  • Organizer: 日本がん転移学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-07-24
• [Presentation] MT1-MMPによる細胞外マトリックス再構築誘導 (2008)
  • Author(s): 小澤晃正, 佐藤博
  • Organizer: 日本がん転移学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2008-07-24
• [Presentation] MT1-MMP活性制御機構の解析 (2008)
  • Author(s): 佐藤博
  • Organizer: 日本分子生物学会年会・日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 細胞接着斑におけるMT1-MMPの役割 (2007)
  • Author(s): 竜野 隆久
  • Organizer: 第80回 日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] 細胞接着斑におけるMT1-MMPの役割 (2007)
  • Author(s): 滝野隆久、佐藤博
  • Organizer: 第80回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-06
• [Presentation] TIMP-2キメラタンパクによるMT1-MMPを介したMMP-2活性化の促進 (2007)
  • Author(s): 内原 嘉仁
  • Organizer: 第66回 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] 細胞接着斑におけるMT1-MMPの役割 (2007)
  • Author(s): 柘植 尚志
  • Organizer: 第66回 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] MT1-MMPによるGDF15切断の生理的意義の解析 (2007)
  • Author(s): 佐藤博、遠藤良夫、滝野隆久
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] MT1-MMP阻害変異体の細胞接着斑への標的は腫瘍細胞の浸潤抑制を増強する (2007)
  • Author(s): 滝野隆久、佐藤博
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] TIMP-2キメラタンパクによるMT1-MMPを介したMMP-2活性化の促進 (2007)
  • Author(s): 内原嘉仁、滝野隆久、佐藤博
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] 細胞接着斑におけるMT1-MMPの役割 (2007)
  • Author(s): 柘植尚志、滝野隆久、佐藤博
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] MT1-MMPによるGDF15切断の生理的意義の解析 (2007)
  • Author(s): 佐藤 博
  • Organizer: 第66回 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] MT1-MMP阻害変異体の細胞接着斑への標的は腫瘍細胞の浸潤抑制を増強する (2007)
  • Author(s): 滝野 隆久
  • Organizer: 第66回 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] グルココルチコイド受容体を介したMT1-MMP遺伝子発現抑制 (2007)
  • Author(s): 佐藤博、宮森久志、滝野隆久
  • Organizer: 第16回日本がん転移学会総会
  • Place of Presentation: 富山
  • Year and Date: 2007-07-09
• [Presentation] 人工的なMMP-2受容体を介したMT1-MMPによるMMP-2活性化 (2007)
  • Author(s): 宮森久志、滝野隆久、佐藤博
  • Organizer: 第16回日本がん転移学会総会
  • Place of Presentation: 富山
  • Year and Date: 2007-07-09
• [Book] がん転移研究の実験手法 (2008)
  • Author(s): 佐藤博
  • Publisher: 金芳堂
• [Book] がん転移研究の実験手法 (2008)
  • Author(s): 佐藤 博
  • Total Pages: 4
  • Publisher: 金芳堂
• [Remarks]
  • URL: http://web.kanazawa-u.ac.jp/~virology/virology.html