EFFECTS OF PROSTACYCLIN ON TUMOR CELL-INDUCED PLATELET-AGGREGATION

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (2) , 450-456
Abstract
Prostacyclin was evaluated for its ability to inhibit tumor cell-induced platelet aggregation (TCIPA) induced by several rodent tumor lines: B16a (melanoma); 3LL (carcinoma): 15091A (adenocarcinoma); and W256 (carcinosarcoma). Aggregation of human platelets by all 4 lines was inhibited by prostaglandin I2 (PGI2) in a dose-dependent manner, with complete inhibition observed at 10 ng/ml. However, higher PGI2 concentrations were required to inhibit aggregation of homologous rat platelets induced by W256 cells. Prostacyclin was compared to other icosanoids known to inhibit platelet aggregation and was found to be 100-fold more potent than prostaglandin E1 [PGE1] or PGD2 and 1000-fold more potent than its stable nonenzymatic metabolite (6-ketoprostaglandin F1.alpha.). PGE2, in contrast to PGE1 and PGD2, did not inhibit TCIPA; however, both PGE2 and its enzymatic metabolite (13,14-dihydro-15-ketoprostaglandin E2) prevented PGI2 inhibition of TCIPA. The addition of PGI2 (100 ng/ml) after initiation of TCIPA (50% of maximum response) resulted in immediate arrest of TCIPA followed by reversal of platelet aggregation. Prostacyclin partially reversed platelet aggregation when added at 100% of maximum response. Platelets enhanced the adhesion of [125I]uridine-labeled W256 cells to plastic culture dishes under both aggregatory and nonaggregatory conditions. Prostacyclin in vitro inhibited platelet-facilitated tumor cell adhesion. These in vitro results demonstrated that PGI2 is a potent inhibitor of TCIPA and of tumor cell adhesion. These are possible mechanisms to explain the antimetastatic effects of PGI2 in vivo.