Proaggregating and procoagulant activities of human mesothelioma tumor cells at different stages of "in vitro" culture

BACKGROUND: The mechanisms of the interactions between tumor cells and the hemostatic system are not completely understood; the purpose of this study was to elucidate whether tumor cells grown "in vitro" express the same proaggregating and procoagulant activities as cells isolated from tumor tissues, and whether the activities of such cultures are constant and consistent over time. METHODS: Tumor cells were collected and cultured from the pleural fluid of a 71-year-old patient with a sarcomatous malignant mesothelioma. Platelet aggregating activity was studied by adding tumor cells to platelet rich plasma or to washed, aequorin-loaded platelets. The procoagulant activity of the tumor cells was measured by the one-stage recalcification time of different humans plasma substrates. RESULTS: Cells harvested after 4 culture passages possessed low, ADP-dependent platelet aggregating activity, while those studied after 16 or 40 passages activated platelets through the production of thrombin. In the washed platelet system and in the presence of trace amounts of platelet poor plasma, the difference in the aggregating activity of various tumor cell populations was more evident. Normal mesothelial cells did not induce platelet aggregation. Procoagulant activity (tissue factor-like) was low in normal mesothelial cells and in tumor cells after 4 passages, and it was about 10 times higher in tumor cells after 16 or 40 passages. CONCLUSIONS: Results obtained with tumor cells cultured "in vitro" should be considered with caution because their effects are different from those of freshly isolated cells and may not be constant in the different culture passages.