Relationship between cellular procoagulant activity and metastatic capacity of B16 mouse melanoma variants

The metastatic process is a complex sequence of steps that may involve coagulation and the presence of fibrin. F1 (low incidence of lung colonization) and F10 (high incidence of lung colonization) variants of the B16 mouse melanoma were used to examine the relationship between the level of cellular procoagulant activity and their metastatic potential. Cell suspensions were prepared from cultures of B16-F1 and B16-F10 cell lines. Aliquots (0.2 ml) containing 50,000 cells were assayed for procoagulant activity in recalcified citrated rat plasma and for metastatic capacity by tail vein injection followed by counting of melanotic lung tumor colonies 17 days later. In one series of experiments, procoagulant activity and metastatic capacity were determined at 1, 2, 3, and 4 days after plating. The data showed an almost parallel decrease in both characteristics as the culture density increased. To examine the correlation between cellular procoagulant activity and the metastatic capacity of the B16 variants in two different series of experiments, regression analysis of the level of procoagulant activity and the number of lung tumor colonies gave correlation coefficients of 0.9 (n = 15) and 0.79 (n = 8). These results suggest that fibrin formation resulting from cellular procoagulant activity may play a role in the metastatic process.