title: Analysis of tissue factor expression in various cell model systems: cryptic vs. active.
abstract: BACKGROUND
  Tissue factor (TF) encryption plays an important role in regulating TF coagulant activity. Potential differences in experimental cell model systems and strategies hampered our understanding of the TF encryption mechanisms.
  
  
  OBJECTIVE
  To characterize the procoagulant activity status of TF in different cell types, and to determine whether increased TF procoagulant activity following the activation stems from transformation of the cryptic TF to the active form.
  
  
  METHODS
  Simultaneous kinetic analyses of TF-FVIIa activation of FX and FVIIa binding to cell surface TF were performed under identical experimental conditions in fibroblast (WI-38), cancer cell (MDA-231), endothelial cell (HUVEC) and monocytic cell (THP-1) model systems. These data were then utilized to estimate TF coagulant-specific activity and percentages of active and cryptic TF present in these cell types.
  
  
  RESULTS
  MDA-231 and WI-38 cells express 10 to 100 times more TF on their cell surfaces compared with perturbed HUVEC and THP-1 cells. TF-specific activity on cell surfaces of MDA-231, WI-38 and THP-1 cells was very similar. Nearly 80-90% of the TF in MDA-231, WI-38 and THP-1 cells was cryptic. A plasma concentration of FVII would be sufficient to bind both active and cryptic TF on cell surfaces. Increased TF activity following cell activation stems from decryption of cryptic TF rather than increasing the coagulant activity of the active TF.
  
  
  CONCLUSIONS
  Our data demonstrate that TF encryption is not limited to a specific cell type, and unlike previously thought, the majority of the TF expressed in cancer cells is not constitutively procoagulant.
authors.affiliation: Department of Cellular and Molecular Biology, Center for Biomedical Research, The University of Texas Health Science Center at Tyler, TX 75708, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kothari
authors.forename: U R
authors.initials: UR
authors.lastname: Pendurthi
authors.forename: L V M
authors.initials: LV
authors.lastname: Rao
mesh_terms: D001777:Blood Coagulation; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D015942:Factor VIIa / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000378:metabolism*; D015398:Signal Transduction; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D013925:Thromboplastin; D015942:Factor VIIa; D015951:Factor Xa
keywords: blood coagulation factors; cells; factor VIIa; hemostasis; phospholipids; tissue factor