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American Red Cross Blood Services Laboratories, Bethesda, Maryland 20814
Three different mechanisms have been detected for the aggregation of platelets by tumor cells in a homologous human system based on inhibition studies with apyrase, hirudin, and phospholipase D. In the major group, platelet aggregation induced by the SKBR3 (adenocarcinoma), SKNMC (neuroblastoma), HT29 (adenocarcinoma), and HT144 (melanoma) cell lines was inhibited by apyrase and phospholipase D but not by hirudin, suggesting that adenosine 5'-diphosphate is involved in the first step. However, since the reaction occurs only in heparinized plasma, the mechanism must differ from that of platelet aggregation which can be induced in citrated plateletrich plasma by endogenous or exogenous adenosine 5'-diphosphate. In contrast, the Hut28 (mesothelioma) line was inhibited by hirudin and phospholipase D but not by apyrase, suggesting that the mechanism in this system involves the activation of the clotting system in the early stages. However, the coagulant-dependent mechanism observed with Hut28 can be differentiated from the similar mechanism we have observed previously with the U87MG (glioblastoma) cell line since the latter is unaffected by phospholipase D (Am J. Hematol., 11: 367378, 1981). Phospholipase C had no effect on platelet aggregation induced by any of the human cell lines examined while both phospholipase A2 and lysolecithin inhibited aggregation in every case. These results suggest that two categories of human tumor cells can be defined based on whether they initiate platelet aggregation by adenosine 5'-diphosphate or coagulant-dependent mechanisms. However, within this latter category, subclassification is possible based on the inhibitory effects of phospholipase D.
1 This work was supported, in part, by USPHS Grants HL 20971, HL 14697, ROICA, 30538 and Biomedical Research Support Grant RR0575. Contribution 515 from the American Red Cross.
2 Permanent address: Hospital Clinico y Provincial, Servicio Hemoterapia y Hemostasia, Universidad de Barcelona, Barcelona, Spain.
3 To whom requests for reprints should be addressed.
Received 4/22/81. Accepted 8/ 4/82.
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