A correlation between
cancer and prothrombotic states has long been described. More recently, a number of studies have focused on the procoagulant mechanisms exhibited by
tumor cells. In the present study, we dissected the molecular mechanisms responsible for the procoagulant activity of MV3, a highly aggressive human
melanoma cell line. It was observed that
tumor cells strongly accelerate plasma coagulation as a result of: i) expression of the blood clotting initiator
protein, a tissue factor, as shown by flow cytometry and functional assays (
factor Xa formation in the presence of cells and
factor VIIa), and ii) direct activation of
prothrombin to
thrombin by cells, as evidenced by hydrolysis of the synthetic substrate,
S-2238, and the natural substrate,
fibrinogen. This ability was highly potentiated by the addition of exogenous
factor Va, which functions as a co-factor for the
enzyme factor Xa. In contrast,
prothrombin activation was not observed when cells were previously incubated with DEGR-
factor Xa, an inactive derivative of the
enzyme. Moreover, a
monoclonal antibody against bovine
factor Xa reduced the
prothrombin-converting activity of
tumor cells. In conclusion, the data strongly suggest that MV3 cells recruit
factor Xa from the culture medium, triggering an uncommon procoagulant mechanism.