Quantitation of fibrinogen influx and fibrin deposition and turnover in line 1 and line 10 guinea pig carcinomas

Abstract

Radiolabeled guinea pig fibrinogen (GPF) was used to measure fibrinogen influx and fibrin accumulation in line 1 and line 10 hepato- (bile duct) carcinomas growing in the s.c. space of syngeneic strain 2 guinea pigs over the course of 7 days following transplant, an interval of growth uncomplicated by immunological tumor rejection or by significant tumor necrosis. Earlier immunofluorescence studies revealed fibrin deposits in both tumors with line 1 much greater than line 10. In accord with these data, GPF accumulated in both tumors in amounts that matched or exceeded plasma fibrinogen levels. Line 1 tumor GPF content was 4-fold greater than that of line 10 tumors and 11- to 33-fold that of normal s.c. tissue. The composition of tumor fibrinogen-fibrin was investigated by aqueous and urea extraction. The fraction of total accumulated GPF that was urea insoluble, and therefore presumably cross-linked fibrin, was constant over time but strikingly different for line 1 (65%) and line 10 (48%) tumors, as compared with control s.c. tissue (18%). By 7 days, line 1 tumors (mean weight, 0.77 g) contained nearly 2 mg of fibrinogen-fibrin, and line 10 tumors (mean weight, 0.62 g) contained nearly 0.5 mg. Influx of GPF and initial clotting were constant over time and equivalent for the two tumors. Hence, the large differences in GPF accumulation observed between these tumors apparently reflect differences in fibrinolysis, not in fibrinogen influx or coagulation. The data presented indicate substantial traffic of plasma fibrinogen into and out of both tumors, as compared with control tissues, equivalent to nearly 10 and 7 ml of plasma over 7 days of growth for line 1 and line 10 tumors, respectively; comparable values for normal s.c. tissues were 1.0 to 1.4 ml plasma fibrinogen. Even in line 1 tumors with their abundant fibrin gel, only 6.3% of GPF entering tumors over 7 days was retained, as compared with 2% for line 10 tumors and approximately 1% for control tissue.