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• W2967214804 abstract "5852 Oncogenic events affect tumor initiating cancer stem cells (CSCs), but also play a significant role in tumor-host interrelationships, including cancer-related Trousseau syndrome, angiogenesis and metastasis. It is of note that some of the latter events are attributed to the procoagulant cell membrane receptor known as tissue factor (TF), or thromboplastin. TF binds the clotting factor VIIa and thereby activates the coagulation cascade. At the same time TF also triggers intracellular signalling, gene expression and alters cellular behaviour. Collectively, this raises the question as to the possible relationship between CSCs and TF in cancer.
 Our studies show that cancer cells frequently upregulate TF downstream of several different oncogenic events. In A431 squamous cell carcinoma cells driven by the amplification of the epidermal growth factor receptor (EGFR) TF levels are controlled by this genetic lesion. This is evident from the fact that in this context EGFR inhibitors downregulate TF expression and procoagulant activity and also suppress tumor growth and angiogenesis in vivo. At the same time in the subset of A431 cells, which express high levels of CD133 (a marker of CSCs) we observed several fold greater TF activity than in the corresponding CD133-negative tumor cell population. It is of interest whether high and sometimes heterogenous TF expression can also be linked to the CSC subset in other cell lines and tumors. Notably, in some of these instances tumor growth/take can be inhibited by the administration of TF inhibitors.
 Host TF also plays a role in tumor growth. Thus, while TF expressing cancer cells readily form tumors in mice hypomorphic for this receptor, cells rendered TF-deficient fail to grow in such recipients. We postulate that activation of the coagulation system and TF signaling, may deliver growth-promoting stimuli (e.g. fibrin, thrombin, platelets) to dormant CSCs and thereby facilitate tumor take, growth, angiogenesis and metastasis.
 In summary, TF may be expressed by CSCs and provide them with the capacity to generate provisional (coagulation-related) cancer stem cell niche due to stimulating influences of coagulation proteases, growth factors and the fibrin matrix. Alternatively, these CSC growth/survival-promoting activities may be associated with the intercellular TF transfer, as cargo of microvesicles, or are delivered in a paracrine manner i.e. by various 9activated9 elements of the tumor stroma (blood vessels, inflammatory cells and mesenchymal cells). Thus, targeting TF may diminish the potential of CSCs to initiate tumor growth, metastasis or recurrence." @default.
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• W2967214804 date "2008-05-01" @default.
• W2967214804 modified "2023-09-28" @default.
• W2967214804 title "The role of tissue factor and the coagulation system in the function of tumor initiating (stem) cells" @default.
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