Relationship between tissue factor and tumor blood vessels

By | January 2, 2012

1971 J. Folkman found that the proliferation of solid tumors, metastasis must first angiogenesis, inhibit tumor angiogenesis as a new method for the treatment of cancer. Thereafter, angiogenesis and tumor biological behavior of tumors is increasingly becoming a hot spot.Relationship between tissue factor and tumor blood vessels, there are a lot of basic research and clinical trial confirmed that a solid tumor angiogenesis, development and transfer of the key.
Angiogenesis in two ways: one is dependent pathway of coagulation, TF expression through activation of thrombin, which leads to the formation of blood vessels; the other is non-dependent coagulation pathway, through activation of VEGF, bFGF to cause angiogenesis. TF on angiogenesis may have a role in two ways.
Relationship between tissue factor and tumor blood vessels, non-dependent mechanism in the coagulation, TF induced angiogenesis there are two different ways.
(1) TF induced angiogenesis is not dependent on the generation of thrombin and fibrin deposition in the cytoplasm of TF receptor serine residue is phosphorylated by PKC pathway, not dependent on ligand binding. Major role in receptor phosphorylation of the downstream signaling pathway, resulting in transcriptional activation or inactivation of other genes. VEGF, an early angiogenic factors, can be activated by the TF regulation; while thrombospondin -1, an anti-angiogenic factor, can be activated by a reduction in TF. VEGF, in turn, increases the production of TF, this vicious cycle to promote tumor growth and the formation of blood coagulation. VEGF can also increase the permeability of blood vessels and lead to leakage of plasma proteins in tumor cells and endothelial cells around the fibrin-rich matrix deposition in early angiogenesis. Increase in VEGF and platelet-reactive protein -1 reduction can cause the proliferation of endothelial cells, and ultimately can lead to tumor angiogenesis. TF and its ligand binding factor VII, activated factor VII (FVIIa), and increase the intracellular calcium concentration. Intracellular calcium can activate PKC, and phosphorylation of TF cytoplasmic tail of receptors. Ligand binding can also promote the adhesion of ABP-280 tail, causing the assembly of muscle fiber white silk. Related to this MAPK signaling pathway and regulation of FAK phosphorylation and downstream signaling pathways can promote the adhesion of endothelial cells, TF and tumor angiogenesis necessary for migration.
(2) TF can be induced angiogenesis through the generation of thrombin, not dependent on the aggregation of fibrin deposition and formation of active TF receptor ligand with its back to the combination of factors. Factor VII is activated the formation of TF / FVIIa complex further activates factor X (FX a). If you can not bind to tissue factor pathway inhibitor / stop the TF / FVII a / FX a compound, activated factor X isolated from the complex down there with the other phospholipid membrane calcium ions combine, and activated to Since the prothrombinase complex factors, which can convert the thrombin clotting factors. Thrombin cleavage generated N-terminal part of the regional expression of PARs is a new N-terminal end, and its function is a limited ligand. This limited cell ligand is a group of seven transmembrane G protein with the second transmembrane domain receptors. Thrombin cleavage of PAR-l, PAR 3, PAR-4, but not hydrolysis PAR-2. Other proteases, such as membrane insulin, type membrane protein, TF / FWa complex, or the FX a, to activate PAR-Z. Activation of PARs can lead to conformational changes, restricted to the GTP-related G protein changes in GDP. G protein contains a unit, which has nucleotide binding site and an R and dimer. Tissue expression of different G protein molecules, which play different roles of thrombin. PAR due to special signal to activate transcription dependent on G proteins and PAR adhesion. Transcription signals, such as MAPKs, can lead to transcriptional activation of many genes which led to the formation of blood vessels. Thrombin activation of PARs causes upregulation of many angiogenic genes including VEGF, VEGF receptor, TF, bFGF and MMP-2.
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