The process of tumor invasion and metastasis factors, a large literature shows that, urokinase-type plasminogen activator (uPA system) and tumor closely related to humans, including leukemia are associated with a variety of tumors overexpressed uPA and uPAR such as breast cancer, liver cancer , colon cancer, lung cancer , bladder cancer, adenocarcinoma, and glioblastoma film and so on.
The process of tumor invasion and metastasis factor (a) of the regulation of extracellular proteolytic processes
uPA as a protease can activate plasminogen to generate the active plasmin. The role of fiber in a variety of sea-enzyme substrate can not only degrade the various ECM components, also can activate a variety of precursor forms of matrix metalloproteinases, further amplification reaction of degradation of ECM to promote tumor cell invasion and metastasis.
The presence of cells not only promoted the pro-uPA and plasminogen activation of each other, but also promote plasmin-catalyzed pro-uPA to uPA and uPA-catalyzed changes in the original activation of fiber quietly. Promote cell surface plasminogen activation requires not only the combination of uPA and uPAR, but also with other cell surface plasminogen binding molecules. This may be due to plasminogen, uPA binding to the cell surface such as the formation of a higher concentration and effective Board Post spatial components, and then a variety of catalytic reactions for the cell surface acceleration possible. Plasminogen binding on the cell surface can be attacked from its plasma inhibitor, but the combination of uPA and uPAR are still likely to be its specific inhibitor PAI-I, PAI-2 inactivation.
Recent studies have found, uPAR and 1 integrin interactions not only by regulating extracellular proteolysis and integrin dependent cell migration, but also can promote tumor cell proliferation. In the study of cell model used for the Hep3 cells, the cells with high malignant, rapidly growing, higher levels of uPAR expression and the active form of ERK. In these cells, reduced the expression of uPAR can significantly inhibit ERK activation, and lead to tumor dormancy. uPAR live on ERK through uPAR interaction with the integrin 51, and uPAR and leveling were all co-prime 51 and its ligand (uPA and Vn) combination of circumstances, this activation of the most significant.
The process of tumor invasion and metastasis factor (b) of the regulation of cell migration
In years past, it has been recognized, uPA in a variety of different types of cells have a chemotactic effect. Although nearly all of the chemotactic effect of the realization of the binding to its receptor are required, but according to the need for the involvement of uPA catalytic activity, the chemotaxis has been divided into two types. By proteolysis, uPA can directly activate the zymogen forms of hepatocyte growth factor (pro-HGF), also indirectly by activating plasminogen activation of basic fibroblast growth factor (bFGF) and transforming growth factor, in order to observe cell migration. But in most other cases, it seems that does not require uPA catalytic activity, because there was no proteolytic activity of uPA, and the lack of catalytic domain of uPA fragments can be effectively induced cell motility. uPA protease activity is not dependent on the chemotactic capacity depends on the binding to its receptor, at least in the case of fibroblasts. Because the chemotactic effect was inhibited by antibodies against uPAR, and uPAR expression in the absence of cells not observed. In short, in cells, uPA and uPAR on the cell membrane makes the combination of signals can be passed, and enhance the ability of cell movement. The combination of uPA and uPAR and can be transient activation of multiple signaling molecules.