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Semin Thromb Hemost 2005; 31(3): 356-363
DOI: 10.1055/s-2005-872444
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Plasminogen Activator Inhibitor Type 1 Promotes Fibrosarcoma Cell Migration by Modifying Cellular Attachment to Vitronectin via αvβ5 Integrin

Tsuyoshi Takahashi1 , Kazuya Suzuki1 , Hayato Ihara2 , Hideo Mogami2 , Teruhisa Kazui1 , Tetsumei Urano2 , 3
  • 1First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka
  • 2Second Department of Physiology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
  • 3Professor
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Publication History

Publication Date:
28 July 2005 (online)

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ABSTRACT

Both urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) are associated with a poor prognosis in cancer patients. We demonstrate that PAI-1 inhibits human fibrosarcoma cell (HT-1080) adhesion to vitronectin (Vn) via αvβ5 integrin, and stimulates cell migration from Vn toward collagen type IV (Col). The cells attached more strongly to Vn and Col than to fibronectin (Fn), whereas PAI-1 interfered with cell attachment to Vn only. An integrin antagonist, RGD peptide, and anti-αvβ5 integrin antibodies, which similarly inhibited cell attachment to Vn, also stimulated cell migration from Vn toward Col. u-PA did not modify cell attachment directly, but reversed the PAI-1-mediated inhibitory effect on cell adhesion to Vn, and its stimulatory effect on cell migration from Vn toward Col. Thus HT-1080 cell migration appears to be modified by u-PA and PAI-1, altering cell adhesion to Vn via αvβ5 integrin. This may be related to their tumor-promoting effect.

KEYWORDS

PAI-1 - u-PA - αvβ5 integrin - cell migration

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Tetsumei UranoM.D. Ph.D. 

Second Department of Physiology, Hamamatsu University School of Medicine

1-20-1, Handayama, Hamamatsu

Shizuoka 431-3192, Japan

Email: uranot@hama-med.ac.jp