CHARACTERIZATION OF PLATELET-AGGREGATION INDUCED BY PC-3 HUMAN PROSTATE ADENOCARCINOMA CELLS AND INHIBITED BY VENOM PEPTIDES, TRIGRAMIN ANDRHODOSTOMIN

PC-3 cells, a metastatic human prostate adenocarcinoma line, caused do se-dependent platelet aggregation in heparinised human platelet-rich p lasma (PRP). PC-3 tumour cell-induced platelet aggregation (TCIPA) was completely inhibited by hirudin (5 U/ml) and limited by increasing co ncentrations of apyrase. This TCIPA was unaffected by cysteine protein ase inhibition with E-64 (10 mu M), but was limited by cell. pretreatm ent with phospholipase A(2). PC-3 cell. suspension caused marked, dose -dependent decreases in plasma recalcification times using normal, Fac tor VIII-deficient and Factor IX-deficient, but not Factor VII-deficie nt, human plasma. This effect was potentiated in cell lysates, but was inhibited in intact cells preincubated with sphingosine. Overall, the se data suggest that PC-3 TCIPA arises from PC-3 tissue factor activit y expression. Trigramin and rhodostomin, RGD-containing snake venom pe ptides which antagonise the binding of fibrinogen to platelet membrane glycoprotein IIb-IIIa, prevented PC-3 TCIPA. Similarly, synthetic pep tide GRGDS as well as monoclonal antibodies against platelet membrane glycoproteins IIb-IIIa and Ib prevented PC-3 TCIPA, which was unaffect ed by control peptide GRGDS. On a molar basis, trigramin (IC50, 0.11 m u M) and rhodostomin (IC50, 0.03 mu M) were approximately 5000 and 180 00 times, respectively, more potent than GRGDS (IC50, 0.56 mM). (C) 19 96 Elsevier Science Ltd