Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, some of the current literature on the regulation of proteolysis and angiogenesis during tumor invasion is discussed. Due to the critical location of brain tumors, an understanding of tumor cell interactions with the local environment is particularly relevant. Tissue breakdown during tumor invasion is associated with proteolytic activity, mediated by tumor cells, and surrounding host cells. This review covers two classes of proteinases and inhibitors that have commonly been associated with tumor invasion i.e., plasminogen activator (PA)/plasmin and matrix metalloproteinases (MMP) with special emphasis on the MMP inhibitors, TIMP-1 and TIMP-2. At different steps of the metastatic process, tumor cells interact with endothelial cells. Tumor cells also stimulate the formation of new vessels through the expression of specific angiogenic molecules. At least eight angiogenic molecules have been purified, sequenced and cloned, four of which are discussed here. Regulation of angiogenic activity has been the focus of intense studies recently, and a wide range of synthetic and natural angiogenesis inhibitors have been discovered. Targeting of angiogenic molecules and tumor vasculature may prove useful in future cancer therapeutic strategies.
 ...
PMID:Tumor invasion, proteolysis, and angiogenesis. 752 88

The expression of different components of the plasminogen activator (PA)/plasmin system was explored in a series of colorectal neoplasia. We have found that urokinase (uPA) and urokinase receptor (uPA-R) gene expression is upregulated in adenomas and carcinomas, and that uPA/uPA-R production is confined to stromal cells in the proximity of epithelial proliferations. In addition, in adenomas, the focal increase in uPA mRNA is not systematically coupled to detectable enzymatic activity, whereas in carcinomas, uPA mRNA accumulation is consistently associated with detectable but variable levels of enzymatic activity. In contrast, in the tumor vasculature, tissue-type plasminogen activator-mediated proteolysis is considerably reduced when compared to normal mucosal and submucosal vessels; this reduction in plasmin formation appears to result from the highly increased production of plasminogen activator inhibitor type 1 by endothelial cells. Our observations demonstrate that colorectal neoplasia are associated with marked alterations in the extracellular proteolytic balance controlled by the PA/plasmin system. They show that contrasting disturbances in plasmin formation take place in distinct stromal compartments but not in epithelial cells, and that these disturbances are maximal during invasive neoplasia. Altogether, our results raise the possibility that alterations in plasmin formation should not be exclusively regarded as promoters of cancer cell invasiveness.
 ...
PMID:Plasmin-catalyzed proteolysis in colorectal neoplasia. 755 50

Rearrangement of the skin during wound healing depends on plasmin and plasminogen, which serve to degrade fibrin depositions in the provisional matrix and thereby facilitate keratinocyte migration. In the current study, we investigated whether plasmin and plasminogen likewise played a role during the development of skin cancer. To test this, we set up a chemically induced skin tumor model in a cohort of mice and found that skin tumor growth in Plg(-/-) male mice was reduced by 52% compared with wild-type controls. Histological analyses suggested that the growth-restricting effect of plasminogen deficiency was due to thrombosis and lost patency of the tumor vasculature, resulting in tumor necrosis. The connection between plasmin-dependent fibrinolysis, vascular patency, and tumor growth was further substantiated as the effect of plasminogen deficiency on tumor growth could be reverted by superimposing heterozygous fibrinogen deficiency on Plg(-/-) mice. Tumors derived from these Fib(-/+);Plg(-/-) mice displayed a significantly decreased level of tumor thrombosis compared with Plg(-/-) mice. In summary, these data indicate that plasmin-driven fibrinolysis facilitates tumor growth by maintaining patency of the tumor vasculature.
 ...
PMID:Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner. 2281 83