The Role of VEGF in Oncology: Effects on Hemostasis and Thrombosis

Department of Medical Oncology, VUMC P.O. Box 7057 Amsterdam (The Netherlands) Tel. 31 20 4444303, Fax 31 20 4444081, E-Mail hm.pinedo@azvu.nl Angiogenesis is essential for tumor growth and metastasis [1]. One of the key players in the angiogenic process is vascular endothelial cell growth factor (VEGF), which exerts its effects through in particular VEGFR-1 (Flt-1 murine homologue) and VEGFR-2 (KDR human homologue; Flk-1 murine homologue) located on endothelial cells (ECs) [2]. These well known effects include increased permeability, proliferation and migration of ECs. However, VEGF also affects hemostatic properties of ECs by inducing the rapid release of von Willebrand factor (vWF), by increasing the expression of tissue factor (TF) and thrombomodulin (TM), and by modifying fibrinolysis due to the stimulation of the expression levels of tissue-plasminogen activator (t-PA), urokinase-plasminogen activator (u-PA), plasminogen activator inhibitor-1 (PAI-1) and the receptor for u-PA (u-PAR) [3–13]. VEGF stimulated ECs furthermore promote adhesion and activation of platelets [9]. On the other hand, platelets are transporters of among other factors VEGF and have most likely a role in tumor induced angiogenesis [14, 15]. This hypothesis has been confirmed by the finding of very high concentrations of both VEGF and coagulation factors in tumor fluid of soft tissue sarcomas [16]. There is growing evidence that coagulation, platelets and angiogenesis are indistinguishable involved in tumor growth. The Role of VEGF in Oncology: Effects on Hemostasis and Thrombosis