We have evaluated in a homologous system the mechanisms of platelet activation by cells isolated from fresh human
tumor tissues and the role of
thromboxane B2 (TxB2) generation in this process. Thirty-eight of the 46
tumor tissues considered showed a high platelet-aggregating activity, with no particular distribution in any specific
tumor type.
Apyrase caused a nonsignificant reduction in the aggregation response,
hirudin did not change it, while
iodoacetic acid or
p-hydroxymercuriphenylsulfonate, specific
cysteine proteinase inhibitors, significantly reduced the platelet-aggregating capacity of these
tumor cells. In 9 colon
carcinomas and in 8
breast carcinomas the levels of TxB2 produced by platelets after addition of
tumor cells were measured:
tumor cell-induced platelet aggregation was accompanied by a significant production of the metabolite;
indobufen, a
cyclooxygenase inhibitor, significantly reduced aggregation and particularly TxB2 production, while the
drug had no effect on both parameters if preincubated with
tumor cells only. These data suggest that cells isolated from different human
tumor tissues activate platelets through the activity of
tumor-associated
cysteine proteinase(s); platelet aggregation by
tumor cells is largely dependent on
arachidonic acid metabolism in platelets, while such metabolism in
tumor cells does not play a significant role.