Evidence of a warfarin-sensitive cancer procoagulant in V2 carcinoma

Rabbit V2 carcinoma tissue is the tumor in which cancer procoagulant activity (CP) was first described, purified and identified as a cysteine proteinase able to activate F X directly. In the present study we show that CP of V2 carcinoma extracts is depressed in its biological activity (although the antigen is present) by warfarin treatment. The biochemical basis for this effect is offered by the identification of Vit.K-dependent gamma-carboxylase in the microsomal fraction of the tumor tissue. V2 carcinoma tissue had very low endogenous substrate(s) of tumor carboxylase in basal conditions but this increased threefold after warfarin. The accumulation of endogenous substrate(s) and the depression of the CP activity by warfarin raises the possibility that CP represents at least one of the substrates for gamma-glutamyl carboxylase in this experimental tumor tissue.