ABSTRACT

Tumors may activate platelets via several mediators, such as adenosine diphosphate (ADP), but thrombin, the most potent physiological activator of platelets, is probably the most important among them. Tumor cells cause thrombin generation by producing tumor-associated tissue factor (TF), which is not usually expressed on normal epithelial cells and may be further upregulated in hypoxic states, such as within tumor tissue.61 Thrombin activates platelets, leading to overexpression of GP IIb/IIIa, vWF, P-selectin and other adhesive molecules, such as fibronectin (Fn). Therefore, it is not surprising that thrombin-pretreated platelets enhance the adhesion of tumor cells to them.55 However, thrombin treatment of tumor cells (human colon carcinoma, murine melanoma, and several other cell lines) also increases platelet-tumor cell adhesion.62,63 Several melanoma cell lines show enhanced binding to platelets and to the adhesive ligands Fn and vWF by a ‘GP IIb/IIIa-like’ receptor.64,65 The presence of and the requirement for thrombin-enhanced binding to platelets66 and pulmonary metastasis67 of protease-activated thrombin receptor (PAR-1) have been shown recently.