Inactivation of factor Va by activated protein C on selected human tumor cell lines.
Previous studies have demonstrated that platelets or aortic endothelial cells provide an appropriate surface that augments the proteolytic inactivation of factor Va by activated protein C (APC). We have examined the ability of three human tumor cell lines (HepG2, CAPAN-2 and J82) to support the inactivation of human factor Va by human APC in the presence and absence of human protein S. APC-mediated factor Va inactivation on these tumor cell lines was assessed by measuring the ability of residual cell-bound factor Va to augment the proteolytic activation of prothrombin by factor Xa. Each of the tumor cell lines studied supported factor Va inactivation by APC in the presence of calcium ions. HepG2 cell monolayers supported this reaction most effectively, with CAPAN-2 and J82 cell monolayers exhibiting moderate and weak effectiveness, respectively. Although not essential for this reaction, protein S moderately enhanced the rate of factor Va inactivation by APC on these tumor cell lines. In addition, pretreatment of each tumor cell line with rabbit antihuman protein S IgG had little, if any, effect on its ability to support factor Va inactivation by APC. Our data suggest that these, and perhaps other, tumor cells can provide an appropriate phospholipid surface for promoting factor Va binding and rapid inactivation by APC.
Nakagaki
T
T
Department of Pathology, University of New Mexico, School of Medicine, Albuquerque 87131.
Sueyoshi
T
T
Kisiel
W
W
D002118:Calcium / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005165:Factor V / Q000378:metabolism; D015943:Factor Va / Q000037:antagonists & inhibitors*; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011486:Protein C / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology*
D009363:Neoplasm Proteins; D011486:Protein C; C022475:prothrombinase complex; D015943:Factor Va; D005165:Factor V; D005170:Factor X; D015951:Factor Xa; D002118:Calcium