Absence Of Role For Platelet-Derived ADP In Tumor Cell-Induced Platelet Aggregation

Interaction with platelets is thought to be a major factor in the metastatic dissemination of human tumors. Previous studies using non-human lines have suggested that aggregation induced by tumor cells is dependent on the release of platelet-derived ADP. We have re-examined this phenomenon in heparinized platelet rich plasma with two human tumor cell lines: Hut 20 derived from a large cell carcinoma of the lung and U87MG derived from a glioblastoma, U87MG caused a single irreversible wave of aggregation simultaneously with the onset of platelet secretion and was inhibited by heparin and hirudin but not by apyrase. In contrast the Hut 20 line gave an initial reversible wave followed by a second irreversible wave which then led to secretion. Aggregation was unaffected by heparin or hirudin but was inhibited by apyrase. Blockage of the cyclooxygenase pathway and platelet secretion by aspirin did not affect the first wave of Hut 20-induced aggregation but gave moderate reductions in the second wave (∼50%) and with U87MG (∼25%). With both cell lines, aggregation was completely blocked by protease inhibitors, and by removal of Ca⁺⁺ and did not occur with gel-filtered platelets. These results suggest that platelet aggregation by the Hut 20 line is induced by ADP released from the tumor cell themselves while aggregation induced by the U87MG line is dependent on the development of a procoagulant activity of the tumor cell surfac.