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Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for ProMMP-2 generates active MMP-2
- フォーマット:
- 論文
- 責任表示:
- Nishida, Yuki ; Miyamori, Hisashi ; Thompson, Erik W. ; Takino, Takahisa ; Endo, Yoshio ; Sato, Hiroshi
- 言語:
- 英語
- 出版情報:
- American Association for Cancer Research, 2008-11-01
- 著者名:
Nishida, Yuki Miyamori, Hisashi Thompson, Erik W. Takino, Takahisa Endo, Yoshio Sato, Hiroshi - 掲載情報:
- Cancer Research
- ISSN:
- 0008-5472
- 巻:
- 68
- 通号:
- 21
- 開始ページ:
- 9096
- 終了ページ:
- 9104
- バージョン:
- author
- 概要:
- 金沢大学がん研究所がん病態制御<br />The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP (MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP- … 2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2-free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal-regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2. ©2008 American Association for Cancer Research.全文公開200911 続きを見る
- URL:
- http://hdl.handle.net/2297/12472
類似資料:
金沢大学がん研究所 = Kanazawa University Cancer Research Institute | |
Japanese Cancer Association / Oxford University Press |
日本生化学会 = Japanese Biochemical Society |
Japanese Cancer Association / Blackwell Publishing Ltd | |
Japanese Cancer Association = 日本癌学会 / John Wiley & Sons |
金沢大学がん研究所 = Kanazawa University Cancer Research Institute |
Japanese Cancer Association / Blackwell Publishing Ltd |
金沢大学がん研究所 = Kanazawa University Cancer Research Institute |