Role of heparin in tumor cell-induced platelet aggregation

B16 mouse melanoma cell lines (B16F1, B16F10 and B16BL6) were able to induce platelet aggregation, and concomitant release of ATP in heparinized platelet-rich plasma (PRP). In citrated PRP, these tumor cells did not induce platelet aggregation. Addition of heparin to citrated PRP enabled these tumor cells to induce aggregation. In heparinized PRP, platelet aggregates induced by B16F10 cells were dissociated by the addition of either 4 mM EDTA, 10 mM CaCl2 or 0.1 micrograms/ml protamine sulfate. B16F10-induced aggregation in heparinized PRP was inhibited by preincubation with anti-fibronectin antibody, but not with antifibrinogen or anti-von Willebrand factor antibodies. B16F10 cells induced aggregation in washed platelet suspension with the addition of heparinized platelet-poor plasma (PPP). Cryoprecipitate from human plasma showed the same effect in the presence of heparin if substituted for PPP. The mixture of purified fibronectin, von Willebrand factor, fibrinogen and heparin were less effective than cryoprecipitate on B16F10-induced aggregation of washed platelets. The results suggest that an interaction between fibronectin and heparin may be important in tumor cell-induced aggregation.