Procoagulant activity of the MC28 fibrosarcoma cell line in vitro and in vivo.
Experimental evidence suggests that many tumours can activate blood coagulation and that such interaction is part of the pathology of metastatic tumour growth. This study aimed to study the procoagulant activity of the methylcholanthrene-induced (MC28) fibrosarcoma to determine whether coagulation activation by these cells could explain the previously reported effects of oral anticoagulants on lung seeding in this model. MC28 cells shortened the recalcification times of normal and factor VII-deficient plasma and directly activated factor X in a chromogenic assay, but did not aggregate platelets in vitro in either whole blood or platelet-rich plasma. Cellular coagulant activity was calcium-dependent, blocked by DFP and concanavalin A but not inhibited by iodoacetamide, E-64 or antibodies to human tissue factor or factor VII. Injection of viable MC28 cells into hooded Lister rats induced a decrease in platelet count (P < 0.001), plasma factor X (P < 0.001) and fibrinogen (P < 0.05) and a marked increase in plasma haemoglobin (P < 0.001). These effects were either not observed or were considerably less marked in heparinized or warfarinized animals. Injection of MC28 cells treated with concanavalin A in vitro completely abolished the clotting changes observed with untreated cells. In conclusion, MC28 cells possessed a potent factor X-activating serine proteinase procoagulant in vitro, which had some of the characteristics of a tissue factor/factor VIIa complex. In vivo, MC28 cells caused clotting activation and intravascular fibrin generation. Since thrombocytopenia was abolished by heparin and the cells lacked platelet aggregating activity in vitro, thrombocytopenia was probably secondary to intravascular coagulation and thrombin generation. The trigger for intravascular clotting activation appeared to be the cellular procoagulant activity since it was abolished by prior in vitro blockade of the latter with concanavalin A.
Amirkhosravi
M
M
University Department of Haematology, General Hospital, Southampton.
Francis
J L
JL
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D003208:Concanavalin A / Q000494:pharmacology; D005170:Factor X / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005354:Fibrosarcoma / Q000097:blood* / Q000139:chemically induced; D006454:Hemoglobins / Q000032:analysis; D006493:Heparin / Q000494:pharmacology; D008297:Male; D008748:Methylcholanthrene; D010974:Platelet Aggregation / Q000502:physiology; D010976:Platelet Count; D051381:Rats; D014407:Tumor Cells, Cultured; D014859:Warfarin / Q000494:pharmacology
D006454:Hemoglobins; D003208:Concanavalin A; D008748:Methylcholanthrene; D014859:Warfarin; D005170:Factor X; D005340:Fibrinogen; D006493:Heparin