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Role of TF in Cancer Progression

Coagulation-dependent mechanisms 1,2 Mediated through PKC phosphorylation of TF Initiates a signaling cascade that: Activates transcription of VEGF Downregulates anti-angiogenic thrombospondin Induces cytoskeletal mobilization/cell migration. Coagulation-independent mechanisms 3,4

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Role of TF in Cancer Progression

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  1. Coagulation-dependent mechanisms1,2 Mediated through PKC phosphorylation of TF Initiates a signaling cascade that: Activates transcription of VEGF Downregulates anti-angiogenic thrombospondin Induces cytoskeletal mobilization/cell migration Coagulation-independent mechanisms3,4 Deposition of fibrin and platelets around tumor cells promotes angiogenesis Fibrin/platelets seal immature tumor vasculature Fibrin elicits expression of IL-8 and VEGF (angiogenic factors) Fibrin elicits additional expression of TF TF-factor VIIa complex signals through PAR, inducing genes involved in proliferation, migration, angiogenesis Role of TF in Cancer Progression 1. Fernandez PM, Rickles FR. Curr Opin Hematol. 2002;9:401-406. 2. Zhang Y et al. J Clin Invest. 1994;94:1320-1327. 3. Kubota S et al. J Biochem. 2004;136:279-282. 4. Rak W et al. In: Khorana AA and Francis CW, eds: Cancer-associated thrombosis: New findings in translational science. Informa Healthcare. 2008.

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