gamma-Glutamyl carboxylase activity in experimental tumor tissues: a biochemical basis for vitamin K dependence of cancer procoagulant.
Rabbit V2 carcinoma tissues have been described to possess a procoagulant activity with specific characteristics; this material has been purified and identified as a cysteine proteinase able to directly activate coagulation factor X. We have shown here that the procoagulant activity of V2 carcinoma extracts is depressed in warfarin-treated animals, thus suggesting that cancer procoagulant could represent a new vitamin K-dependent protein. The biochemical basis for this effect is offered by the identification of gamma-glutamyl carboxylase in the microsomal fraction of tumor tissues. The V2 carcinoma has a carboxylase activity which is increased in warfarin-treated animals. An endogenous substrate of tumor carboxylase, the nature of which has not been identified, has been found 5-fold increased in warfarin-treated animals. The presence of gamma-glutamyl carboxylase was also described in several murine tumors including both carcinomas and fibrosarcomas. It is worth mentioning that all the tumors tested produce a procoagulant with the peculiar characteristics of that described in V2 carcinoma. It is conceivable that cancer procoagulant could represent at least one of the substrates for gamma-glutamyl carboxylase in these experimental tumor tissues.
D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism; D019735:Carbon-Carbon Ligases; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D011817:Rabbits; D014812:Vitamin K / Q000378:metabolism*; D014859:Warfarin / Q000494:pharmacology
D001779:Blood Coagulation Factors; D009363:Neoplasm Proteins; D014812:Vitamin K; D014859:Warfarin; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase