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 Printable version |
Roles of tissue factor in cancer |
Hématologie. Volume 18, Number 1, 37-46, Janvier-Février 2012, Revue Picto_transfusion
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 Résumé
Texte intégral
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Author(s) : Jérôme Rollin, Yves Gruel |
Summary : Tissue factor (TF) is a glycoprotein that binds factor VII and factor VIIa and triggers coagulation, but it has also been demonstrated that it plays a key role in cancer. Numerous cancer cells express TF, and TF gene is upregulated by several oncogenic events affecting
KRAS and
TP53. TF favors variable processes that are critical for tumor development and metastases, such as adhesion, cell migration, proliferation, and angiogenesis. Most effects of TF are mediated through protein G- coupled protease-activated receptors such as PAR 2, which is activated by FT/VIIa/Xa complexes localized on the surface of cancer and stroma cells, or PAR1 activated by thrombin. TF triggers the formation of fibrin network around tumor cells that prevent their destruction by NK cells and facilitates their trapping in microvessels of the organs, which are the targets of metastases. In addition, thrombin generated in larger amounts in many cancers activates platelets, and induces the endothelial expression of cell adhesion molecules critical for tissue migration of tumor cells. On the other hand, the role of asTF (alternatively spliced tissue factor) that interacts with α
3β
1 and α
vβ
3 integrins, has recently been outlined in tumor angiogenesis. Increased TF expression in tumors is associated with the release in blood of procoagulant microparticles that favor the development of venous thromboembolic complications in cancer patients. In conclusion, considering the key role of TF in the pathogenesis of cancer, this protein could be a promising target for new drugs in the treatment of several cancers. |
Keywords : tissue factor, cancer, thrombosis |
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