Direct analysis reveals an absence of gamma-carboxyglutamic acid in cancer procoagulant from human tissues.
Additional carboxylation of glutamic acid by vitamin K-dependent gamma-carboxylase is a common posttranslational modification of many proteins, including some of blood clotting factors. Vitamin K-antagonists, such as warfarin, are often included in the therapy of malignant disease, decreasing the blood coagulation potential. Cancer procoagulant, a direct blood coagulation factor X activator from malignant tissue, is considered as a vitamin K-dependent protein, so it could serve as one of possible targets for the therapy with warfarin. However, there is still no experimental data demonstrating directly the presence of gamma-carboxyglutamic acid (Gla) in a cancer procoagulant molecule. The presence of Gla in cancer procoagulant isolated from human amnion-chorion membranes and from human malignant melanoma WM 115 cell line was analyzed directly, using specific anti-Gla monoclonal antibodies. There was no detectable amount of Gla in cancer procoagulant isolated from fetal or malignant tissue. Cancer procoagulant from human tissues does not contain Gla-rich domain. The finding indicates that cancer procoagulant is rather a poor target for warfarin therapy of malignant disease.
Kaplinska
Katarzyna
K
Department of Pharmaceutical Biochemistry, Medical University of Lodz, Lodz, Poland.
Mielicki
Wojciech P
WP
D015055:1-Carboxyglutamic Acid / Q000032:analysis* / Q000276:immunology; D000650:Amnion / Q000201:enzymology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000925:Anticoagulants / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000201:enzymology; D002823:Chorion / Q000201:enzymology*; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005170:Factor X / Q000187:drug effects; D005260:Female; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000494:pharmacology; D011247:Pregnancy; D014859:Warfarin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D009363:Neoplasm Proteins; D015055:1-Carboxyglutamic Acid; D014859:Warfarin; D005170:Factor X; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant