EFFECT OF DIFFERENT PLATELET AGONISTS ON INTRACELLULAR FREE CA-CELLS - POSSIBLE ROLE IN TUMOR-GROWTH(+ CONCENTRATIONS IN HUMAN TUMOR)

Modulation of cytoplasmic Ca++ concentration is a mechanism common to signal transduction pathways regulating many cellular phenomena, inclu ding the interactions of tumors with the hemostatic system. We have in vestigated the pro-aggregating and pro-coagulant activities of human t umor cell lines cultured in vitro and the ability of different platele t agonists to induce Ca++ transients in these cells. Cells of a malign ant mesothelioma line activated platelets by a thrombin-dependent mech anism; on the contrary, Hela cells, derived from a uterine cervical ca ncer, possessed ADP-dependent pro-aggregating activity, and DND-IA mel anoma cells did not stimulate platelet aggregation. All cell lines sho wed a tissue-factor-like procoagulant property, more pronounced in mes othelioma cells. Furthermore, ADP was able to induce a transient incre ase in cytoplasmic Ca++ concentration in tumor cells from all lines; c ollagen showed this effect in mesothelioma cells and in Hela cells, an d thrombin was effective only in mesothelioma cells. PAF never induced Ca++ fluxes in any of the cell lines investigated. Finally, the calci um-channel blocker verapamil inhibited agonist-induced Ca++ transients in tumor cells and in vitro tumor-cell growth. These data may help to identify new possible mechanisms of the 2-way interaction of tumors w ith the hemostatic system. (C) 1995 Wiley-Liss, Inc.