Clinical, laboratory, histopathological and pharmacological evidence support the notion that a systemic activation of blood coagulation is often present in cancer patients. Additionally, thrombin was shown to promote tumour progression and metastasis in animals, and epidemiological studies suggest an increased risk of cancer diagnosis after primary thromboembolism. We have proposed that the aforementioned results may be related to our finding that thrombin is a potent activator of angiogenesis. This is a thrombin receptor-mediated event (the receptor is referred to as protease-activate receptor) and is independent of fibrin formation. Many cellular effects of thrombin on endothelial cells can contribute to the angiogenic action of thrombin. (i) Exposure of endothelial cells to thrombin cause a time- and dose-dependent decrease in the attachment of these cells to basement membrane components, with a concomitant increase in matrix metallo-proteinase 2 activation, (ii) Thrombin upregulates the expression of integrin αvβ3, the marker of the angiogenic phenotype of endothelial cells. (iii) Thrombin has chemotactic and aptotactic effects on endothelial cells and upregulates the expression of the vascular endothelial growth factor (VEGF) receptors (KDR and Flt1). Thus, thrombin synergizes with the key angiogenic factor VEGF in endothelial cell proliferation. Furthermore, thrombin enhances the secretion of VEGF and matrix metalloproteinase 9 of PC3 prostate cancer cells. These results can explain the angiogenic and tumour-promoting effect of thrombin and provide the basis for development of thrombin receptor mimetics or antagonists for therapeutic application.
Skip Nav Destination
Article navigation
April 2002
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkAdvertising
Conference Article|
April 01 2002
Mechanism of thrombin-induced angiogenesis
M. E. Maragoudakis;
M. E. Maragoudakis
1
1Medical School, Department of Pharmacology, University of Patras, 261 10 Rio, Patras, Greece
1To whom correspondence should be addressed (e-mail maragoud@med.upatras.gr).
Search for other works by this author on:
N. E. Tsopanoglou;
N. E. Tsopanoglou
1Medical School, Department of Pharmacology, University of Patras, 261 10 Rio, Patras, Greece
Search for other works by this author on:
P. Andriopoulou
P. Andriopoulou
1Medical School, Department of Pharmacology, University of Patras, 261 10 Rio, Patras, Greece
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 05 2001
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (2): 173–177.
Article history
Received:
November 05 2001
Citation
M. E. Maragoudakis, N. E. Tsopanoglou, P. Andriopoulou; Mechanism of thrombin-induced angiogenesis. Biochem Soc Trans 1 April 2002; 30 (2): 173–177. doi: https://doi.org/10.1042/bst0300173
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.