Document Detail


Analysis of tissue factor expression in various cell model systems: cryptic vs. active.
MedLine Citation:
PMID:  23621622     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
H Kothari; U R Pendurthi; L V M Rao
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  11     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-16     Completed Date:  2014-02-07     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  1353-63     Citation Subset:  IM    
Copyright Information:
© 2013 International Society on Thrombosis and Haemostasis.
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MeSH Terms
Descriptor/Qualifier:
Blood Coagulation*
Breast Neoplasms / metabolism*
Cell Line, Tumor
Cell Membrane / metabolism
Factor VIIa / metabolism
Factor Xa / metabolism
Female
Fibroblasts / metabolism*
Human Umbilical Vein Endothelial Cells / metabolism*
Humans
Kinetics
Monocytes / metabolism*
Signal Transduction*
Thromboplastin / metabolism*
Grant Support
ID/Acronym/Agency:
HL1074830/HL/NHLBI NIH HHS; HL58869/HL/NHLBI NIH HHS; R01 HL058869/HL/NHLBI NIH HHS; R01 HL107483/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
9035-58-9/Thromboplastin; EC 3.4.21.21/Factor VIIa; EC 3.4.21.6/Factor Xa
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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