The Production of a Factor X Activator by a Methylcholanthrene-Induced Rat Fibrosarcoma

Abstract

The association between neoplasia and thrombosis has been well documented. We have studied the production of a procoagulant which is a factor X activator in a rat fibrosarcoma model. Extracts of excised tumor were assayed in a one stage clotting assay using normal and factor deficient human plasmas. The activity was not due to tissue factor, as acceleration of clotting was observed in FVII deficient plasma. No activity was noted in FX deficient plasma. The activator was capable of cleaving 125I-FX in the absence or presence of calcium. A radioimmunoassay (RIA) demonstrated a 5,100-fold increase in the levels of FX activation peptide after exposure to sarcoma extract. The FX activation occurs in the absence of calcium although the effect is greatly accelerated in the presence of 5 mM CaCl2. Using a two-stage amidolytic assay, functional activation of FX by the sarcoma was demonstrated. Inhibitor studies suggest that the sarcoma-derived procoagulant is a serine protease. The methylcholanthrene-induced rat sarcoma may serve as a useful model for investigating the regulation and effects of cancer procoagulants.