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Semin Thromb Hemost 2004; 30(1): 63-69
DOI: 10.1055/s-2004-822971
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Role of Thrombin in Angiogenesis and Tumor Progression

Nikos E. Tsopanoglou1 , Michael E. Maragoudakis1 , 2
  • 1Department of Pharmacology, Medical School, University of Patras, 25110 Patras, Greece
  • 2Professor of Department of Pharmacology, Medical School, University of Patras, 25110 Patras, Greece
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Publication History

Publication Date:
22 March 2004 (online)

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Clinical, laboratory, histopathological, and pharmacological evidence support the notion that the coagulation system, which is activated in most cancer patients, plays an important role in tumor biology. Our laboratory has provided evidence that thrombin activates angiogenesis, a process which is essential in tumor growth and metastasis. This event is independent of fibrin formation. At the cellular level many actions of thrombin can contribute to activation of angiogenesis: (1) Thrombin decreases the ability of endothelial cells to attach to basement membrane proteins. (2) Thrombin greatly potentiates vascular endothelial growth factor- (VEGF-) induced endothelial cell proliferation. This potentiation is accompanied by up-regulation of the expression of VEGF receptors (kinase insert domain-containing receptor [KDR] and fms-like tyrosine kinase [Flt-1]). (3) Thrombin increases the mRNA and protein levels of αvβ3 integrin and serves as a ligand to this receptor. Furthermore, thrombin increases the secretion of VEGF and enhances the expression and protein synthesis of matrix metalloprotease-9 and αvβ3 integrin in human prostate cancer PC-3 cells. These results could explain the angiogenic and tumor-promoting effect of thrombin and provide the basis for development of thrombin receptor mimetics or antagonists for therapeutic application.

KEYWORDS

Thrombin - angiogenesis - tumor - VEGF - integrin

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 Prof.
Michael E Maragoudakis

Department of Pharmacology, Medical School, University of Patras

25110 Patras, Greece

Email: maragoud@med.upatras.gr