THE ROLE OF TISSUE FACTOR IN ANGIOGENESIS AND TUMOR PROGRESSION

Disruption of homeostasis in the coagulation system associated with the course of cancer result in a shift of balance towards prothrombotic. Overexpression of tissue factor (TF) in cancer cells promotes tumor neovascularization, metastases and formation of thromboembolic complications. Studies of cancers in vitro and in vivo indicate the correlations between the TF level and the degree of malignancy tumors, invasiveness, the density of blood vessels and the survival rate. Most likely, impaired TF expression in tumor cells are caused, inter alia, by mutations in tumor suppressor genes and oncogenes, hypoxia and the phenomenon of epithelial-mesenchymal transition. Many studies have shown the participation of TF in the formation of new blood vessels. There are two mechanisms of action of TF in the process of tumor angiogenesis: indirectly linked to the process of coagulation and directly associated with phosphorylation of the cytoplasmic domain of tissue factor. It is believed that elevated levels of TF promote tumor progression. Higher expression of TF is observed in metastatic breast cancer or melanoma cells. Tissue factor, influencing the progression of cancer, including angiogenesis, may be one of the potential targets for anticancer therapy.