Thrombomodulin Suppresses Invasiveness of HT1080 Tumor Cells by Reducing Plasminogen Activation on the Cell Surface through Activation of Thrombin-Activatable Fibrinolysis Inhibitor
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- Higuchi Toshiyuki
- Department of Molecular and Cellular Pathophysiology, Showa Pharmaceutical University Laboratory of Health Chemistry, Nihon Pharmaceutical University
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- Nakamura Takashi
- Department of Molecular and Cellular Pathophysiology, Showa Pharmaceutical University
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- Kakutani Hideki
- Department of Molecular and Cellular Pathophysiology, Showa Pharmaceutical University
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- Ishii Hidemi
- Department of Molecular and Cellular Pathophysiology, Showa Pharmaceutical University
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説明
Cell malignancy is negatively correlated with the expression of thrombomodulin (TM), a thrombin receptor expressed on the surface of various cells, including tumor cells. TM accelerates thrombin-activatable fibrinolysis inhibitor (TAFI) activation catalyzed by thrombin. The active form of TAFI (TAFIa) contributes to inhibition of plasmin formation through its carboxypeptidase B (CPB)-like activity. Here, we examined whether TM- and tumor cell-dependent TAFI activation participates in controlling pericellular fibrinolysis and cell invasion. Human fibrosarcoma HT1080 cells retained the ability to activate both prothrombin and plasminogen, but did not express TM. HT1080 cells mediated activation of TAFI in plasma in the presence of soluble-type TM (sTM) through cell-dependent prothrombin activation. HT1080 cells stably expressing TM (TM-HT1080) mediated plasma TAFI activation without added sTM, but HT1080 (wild-type) and Mock-transfected HT1080 cells (Mock) did not. Production of TAFIa suppressed cell-mediated plasminogen activation. Matrigel invasion by wild-type and Mock cells was enhanced two-fold by diluted plasma (10%), whereas the plasma-induced invasion of TM-HT1080 cells (65% of wild-type invasion) was lower than those of wild-type and Mock cells. Cell invasion by TM-HT1080 was partially enhanced by addition of a TAFIa/CPB inhibitor. These results suggest that TM suppresses pericellular fibrinolysis and plasma-induced tumor cell invasion, and that it is mediated, at least in part, by plasma TAFI activation.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 32 (2), 179-185, 2009
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679604763392
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- NII論文ID
- 110007042142
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 9775067
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- PubMed
- 19182372
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可