Procoagulant properties of human MV3 melanoma cells.
A correlation between cancer and prothrombotic states has long been described. More recently, a number of studies have focused on the procoagulant mechanisms exhibited by tumor cells. In the present study, we dissected the molecular mechanisms responsible for the procoagulant activity of MV3, a highly aggressive human melanoma cell line. It was observed that tumor cells strongly accelerate plasma coagulation as a result of: i) expression of the blood clotting initiator protein, a tissue factor, as shown by flow cytometry and functional assays (factor Xa formation in the presence of cells and factor VIIa), and ii) direct activation of prothrombin to thrombin by cells, as evidenced by hydrolysis of the synthetic substrate, S-2238, and the natural substrate, fibrinogen. This ability was highly potentiated by the addition of exogenous factor Va, which functions as a co-factor for the enzyme factor Xa. In contrast, prothrombin activation was not observed when cells were previously incubated with DEGR-factor Xa, an inactive derivative of the enzyme. Moreover, a monoclonal antibody against bovine factor Xa reduced the prothrombin-converting activity of tumor cells. In conclusion, the data strongly suggest that MV3 cells recruit factor Xa from the culture medium, triggering an uncommon procoagulant mechanism.
Geaquinto
D L A
DL
Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Fernandes
R S
RS
Lima
L G
LG
Barja-Fidalgo
C
C
Monteiro
R Q
RQ
D045744:Cell Line, Tumor / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000502:physiology*; D005165:Factor V / Q000494:pharmacology; D015942:Factor VIIa / Q000494:pharmacology; D015951:Factor Xa / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000502:physiology*; D011516:Prothrombin / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
D009363:Neoplasm Proteins; C035876:factor V clotting antigen; D005165:Factor V; D011516:Prothrombin; D013925:Thromboplastin; D015942:Factor VIIa; D013917:Thrombin; D015951:Factor Xa; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant