Evidence for a warfarin-sensitive serum factor that participates in factor X activation by Lewis lung tumor cells.
Mouse Lewis lung (LL) carcinoma cells possess a factor X activator (procoagulant) that is inhibited in vivo by warfarin treatment or diet-induced vitamin K deficiency. This inhibition suggests that vitamin-K-dependent proteins are involved in LL cell activation of factor X. A LL primary tumor clone (LL13) was isolated which contained a warfarin-sensitive vitamin-K cycle of metabolism and expressed factor X procoagulant activity. LL13 cells exposed to media containing warfarin or deficient in vitamin K grew as well as cells in normal media, and activated factor X to similar extents. In contrast, administration of warfarin to mice bearing LL13 cells inhibited factor X procoagulant activity as well as the vitamin K cycle of metabolism in the primary tumors. In relation to LL13 cells grown in media containing fetal bovine serum, those incubated for 20 hr in media containing mouse serum or the sera from LL13-bearing mice exhibited 9- to 10-times higher levels of factor X procoagulant activity. However, LL13 cells exposed to media containing the sera of warfarin-treated LL-13-bearing mice or to barium-sulfate-adsorbed normal mouse serum activated factor X much less efficiently. Collectively, these data suggest that inhibition of vitamin K function in LL cells does not affect the extent of factor X activation and thus the intrinsic factor X procoagulant is not a vitamin-K-dependent protein. They further suggest that both a warfarin-sensitive (vitamin-K-dependent) protein present in normal mouse serum and a LL13 cell component participate in factor X procoagulant activity.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors*; D002460:Cell Line; D003470:Culture Media; D005170:Factor X / Q000378:metabolism*; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D014812:Vitamin K / Q000378:metabolism; D014813:Vitamin K Deficiency / Q000378:metabolism; D014859:Warfarin / Q000494:pharmacology*
D001779:Blood Coagulation Factors; D003470:Culture Media; D014812:Vitamin K; D014859:Warfarin; D005170:Factor X