INTERACTIONS OF TUMORS WITH THE HEMOSTATIC SYSTEM - ROLE OF CALCIUM FLUXES IN PLATELETS AND IN CANCER-CELLS

Background - Modulation of cytoplasmic Ca2+ concentration is a mechani sm common to signal transduction pathways regulating many cellular phe nomena, including the interactions of tumors with the hemostatic syste m. In the present paper we have investigated the role of Ca2+ movement s through biological membranes in the interactions between tumor cells and platelets. Methods - Cells of a human malignant mesothelioma line were cultured in vitro by standard methods. Platelet aggregation and cytoplasmic Ca2+ levels were investigated with a Platelet Ionized Calc ium Aggregometer. Results - In the absence or in the presence of added fibrinogen tumor cells did not induce any aggregation or any change i n ionized calcium levels; in contrast, after addition of trace amounts of platelet poor plasma (PPP) the cells showed a very strong aggregat ing activity, with a significant increase in platelet cytoplasmic: Ca2 + levels. Addition of hirudin, a specific thrombin inhibitor, together with PPP, completely abolished aggregation and Ca2+ changes induced b y tumor cells. Furthermore, both normal mesothelial cells and mesothel ioma tumor cells were able to significantly shorten the recalcificatio n time of normal plasma; this activity was tissue factor like and it w as much higher in neoplastic cells than in their normal counterparts. Finally, thrombin induced a dose-dependent increase in Ca2+ concentrat ion in aequorin-loaded tumor cells, an effect completely inhibited by the calcium channel blocker verapamil (0.3 mM). Conclusion - These dat a may contribute to identifing possible mechanisms of the two-way inte raction of tumors with the hemostatic system.