Factor X-dependent, thrombin-generating activities on a neuroblastoma cell 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 investigated the mechanism of platelet aggregation induced by a human neuroblastoma 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 factor VIIa. The produced FXa formed prothrombinase complex on the cells and activated prothrombin. From experiments on activity inhibition by specific monoclonal as well as polyclonal antibodies, it was concluded that factor V did not constitute this prothrombinase complex. Another cofactor known to constitute prothrombinase complex on some cells, effector cell protease receptor-1 (EPR-1), was not expressed on GOTO cells, suggesting that the cofactor composing FXa-dependent prothrombinase 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'-deoxyuridine for 4 days, GOTO cells differentiated into Schwann-like cells, and both FXase and prothrombinase activities were greatly diminished. Flow cytometric analyses revealed that the decrease of FXase activity should be attributed to the decrease of tissue factor expression on GOTO cells. Because these activities greatly diminished upon cellular differentiation, the expression of both cofactor molecules may be related to the malignant and metastatic nature of the tumor cells.
Inuyama
H
H
Department of Biological Sciences, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Saito
T
T
Takagi
J
J
Saito
Y
Y
D002454:Cell Differentiation; D005165:Factor V / Q000378:metabolism; D005170:Factor X / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007700:Kinetics; D009447:Neuroblastoma / Q000503:physiopathology*; D010974:Platelet Aggregation; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D000077022:Survivin; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D011956:Receptors, Cell Surface; D000077022:Survivin; D005165:Factor V; D005170:Factor X; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa