A correlation between cancer and prothrombotic states has long been described. More recently, a number studies have focused on the procoagulant mechanisms exhibited by tumor cells. In the present study, we observed that MV3, a human melanoma-derived cell line, has a marked procoagulant activity as evidenced by plasma recalcification assays. By means of flow-cytometric and functional (FXa formation in the presence of cells and FVIIa) assays, it was demonstrated that these cells express tissue factor (TF), a potent procoagulant protein. Surprisingly, MV3 cells directly activated prothrombin into thrombin, as evidenced by hydrolysis of the synthetic substrate, S-2238 and fibrinogen clotting. This ability was highly potentiated by FVa, a known FXa cofactor. On the other hand, prothrombin activation was not observed when cells were previously incubated with DEGR-FXa, an inactive derivative of FXa. Also, a monoclonal antibody against bovine FXa decreased the prothrombin-converting activity of tumor cells. These data strongly suggest that MV3 cells recruit FXa from the culture media, resulting in an unusual mechanism responsible, at least in part, for their potent procoagulant activity.

Financial support: CNPq, FAPERJ, FECD, FAF, and FUJB.