Tumor tissue factor and thrombin, tissue factor can induce the generation of thrombin, activate platelets, to produce aggregation, and feedback to promote the aggregation of intravenous and eventually caused the agglutination of fibrin. Thrombin also mediates many cellular responses, including angiogenesis, cracking protein kinase receptor (protease-activated receptors, PARs) to trigger a series of signal transduction pathways. Therefore, in addition to changes in coagulation status of cancer patients, but now that the thrombin in tumor growth and metastasis of Pathobiology one hub. Although the formation of thrombin is considered to be the most important blood clotting factors, but also through the activation of platelets and fibrin deposition to complete, but some of its regulation of cell behavior is not dependent on the aggregation but by the activation and G protein-related The PARs associated signaling pathways.
Tumor tissue factor and thrombin in cancer patients, and thrombin in vivo can be regulated by many factors and promote tumor angiogenesis and induces microvascular permeability, and PKC in vitro can promote dependence, but the morphological and different from the human umbilical vein endothelial cells back. In many physiological conditions, endothelial cells are in a stable condition. In vascular injury, the thrombin is activated, endothelial cell proliferation and migration to promote wound repair. Thrombin addition to the basic features of hemostasis and coagulation, thrombin is a powerful mitogen to promote cell to cell function caused by the change. Therefore, thrombin has been shown to promote some of the biological behavior of tumor is not surprising.
Angiogenesis dependent mechanism both clotting-independent mechanisms are also involved in blood coagulation: clotting-independent mechanism to directly affect the signaling pathway to influence cell function; dependent mechanism of coagulation by the formation of blood clotting to promote tumor cell growth. Meanwhile, the anticoagulant drugs in cancer therapy can be effective in reducing excessive blood clotting in tumor patients and change some of the biological function of the tumor. In the coagulation-independent mechanisms, mainly through PAR activation and subsequent signal transduction to complete, in the clotting mechanism is mainly dependent on platelet activation and fibrin deposition. The newly formed tumor blood vessels leak of innate, so vascular endothelial growth factor (vascular
endothelial growth factor, VEGF) and vascular leakage factors can affect its blood transport. Although plasma fibrinogen in a large molecular weight, but can still leak into the extravascular. Fibrinogen, thrombin generation in a micro-environment, with inflammatory cells and specific receptors on tumor cells or by the combination of hydrolysis. Fibrin in tumor angiogenesis can be seen on the endothelial cells, which can be inflammatory cells or tumor cells with the combination, or deposited in the tumor cells around the matrix as a temporary formation of blood vessels more easily. A skin blood plasma levels of fibrinogen, thrombin hydrolysis of fibrinogen is the first product that allows tumor growth balance is broken, and aggravated the condition of cancer patients. It was reported that cancer patients with normal plasma fibrinogen is doubled. Cross-junction protein (cross-linked fi-brin, XLF) deposition is one of the characteristics of human malignant tumors, including many breast, lung, brain Yang and prostate cancer. In breast cancer and had just occurred in patients with breast tumor tissue samples, XLF have invasive cancer in cases of endothelial cells to express, but in the wake of the breast tumor blood vessels are not found. Many activated blood plasmin and / or thrombin hydrolysis of fibrinogen component and / or XLF early due to anti-angiogenic factors and angiogenic factors whose biological activity can promote wound healing and angiogenesis . Fibrinogen or fibrin component E, in vivo and can stimulate angiogenesis. It was reported that plasma levels of fibrin d dimer increased in the colon Chuan, Yang and breast cancer patients can be used as an indicator of tumor grade. Recent research reported in breast cancer patients, many transfer experiments, tumor burden experiments, kinetic experiments and the survival of patients showed that plasma levels of fibrin d dimer and fibrinogen levels are closely related. Interestingly, serum levels of VEGF, IL-6 and VEGF platelet load in plasma also fibrin d dimer levels are closely related. Hydrolysis or reduction of fibrinogen and fibrin molecule exposed position in favor of cell surface receptor molecules and combine.
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