Vascular endothelial growth factor-stimulated endothelial cells promote adhesion and activation of platelets

Coagulation abnormalities, including an increased platelet turnover, are fr equently found in patients with cancer. Because platelets secrete angiogeni c factors on activation, this study tested the hypothesis that platelets co ntribute to angiogenesis. Stimulation with vascular endothelial growth fact or (VEGF, 25 ng/mL) of human umbilical vein endothelial cells (HUVECs) prom oted adhesion of nonactivated platelets 2.5-fold. In contrast, stimulation of HUVECs with basic fibroblast growth factor (bFGF) did not promote platel et adhesion. By blocking tissue factor (TF) activity, platelet adhesion was prevented and antibodies against fibrin(ogen) and the platelet-specific in tegrin, alpha (IIb)beta (3), inhibited platelet adhesion for 70% to 90%. Th ese results indicate that VEGF-induced platelet adhesion to endothelial cel ls is dependent on activation of TF. The involvement of fibrin(ogen) and th e alpha (IIb)beta (3) integrin, which exposes a high-affinity binding site for fibrin(ogen) on platelet activation, indicates that these adhering plat elets are activated. This was supported by the finding that the activity of thrombin, a product of TF-activated coagulation and a potent platelet acti vator, was required for platelet adhesion. Finally, platelets at physiologi c concentrations stimulated proliferation of HUVECs, indicative of proangio genic activity in vivo. These results support the hypothesis that platelets contribute to tumor-induced angiogenesis. In addition, they may explain th e clinical observation of an increased platelet turnover in cancer patients . Platelets may also play an important role in other angiogenesis-dependent diseases in which VEGF is involved, such as diabetes and autoimmune diseas es. (C) 2000 by The American Society of Hematology.