FACTOR X-DEPENDENT, THROMBIN-GENERATING ACTIVITIES ON A NEUROBLASTOMACELL AND THEIR DISAPPEARANCE UPON DIFFERENTIATION

Some tumor cells induce platelet aggregation in the bloodstream, which has been implicated in tumor metastasis. In this study, we investigat ed the mechanism of platelet aggregation induced by a human neuroblast oma cell line, GOTO. It was revealed that GOTO cells had tissue factor on their surface and converted factor X (FX) to FXa with the aid of f actor VIIa. The produced FXa formed prothrombinase complex on the cell s and activated prothrombin. From experiments on activity inhibition b y specific monoclonal as well as polyclonal antibodies, it was conclud ed that factor V did not constitute this prothrombinase complex. Anoth er cofactor known to constitute prothrombinase complex on some cells, effector cell protease receptor-1 (EPR-1), was not expressed on GOTO c ells, suggesting that the cofactor composing FXa-dependent prothrombin ase activity on GOTO cells is not factor V or EPR-1 but, rather, is an unknown molecule. Upon the culturing in the presence of 5-bromo-2'-de oxyuridine for 4 days, GOTO cells differentiated into Schwann-like cel ls, and both FXase and prothrombinase activities were greatly diminish ed. Flow cytometric analyses revealed that the decrease of FXase activ ity should be attributed to the decrease of tissue factor expression o n GOTO cells. Because these activities greatly diminished upon cellula r differentiation, the expression of both cofactor molecules may be re lated to the malignant and metastatic nature of the tumor cells. (C) 1 997 Wiley-Liss, Inc.