| Background: Transitional cell carcinoma of bladder is one of the most common diseases treated by urologist. Recurrence is common for tumors and 10-15% of tumors progress to invade the underlying muscle layer. Patients with muscle-invasive disense are at high risk for metastases, and recurrence rates are high. Bladder Cancer, like all solid malignancies , is dependent on angiogenesis to grow progressively and metastasize efficiently.The switch to an angiogenic phenotype is an essential step in bladder tumorigenesis.The angiogenic response is determined in part by the balance between angiogenesis inducers and inhibitors within a given micro-environment As normal cells progress to malignancy, they acquire the ability to induce angiogenesis, in part by altering the milieu of secreted angiogenesis mediators to favor a net inductive activity ; on the other hand, these changes are mediated by many other factors, such as HIF, activation of oncogenes or inactivation of tumor suppressor genes .VEGF is a glycosylated multifunctional cytokine that exerts a number of important biological actions on endouthelial cells.lt can increase the permeability of microvessels and induces endothelial cell growth.lt is a potent inducer of angiogenesis.TSP-1 is a 450kd glycoprotein that is an important component of the extracellular matrix and is known to be a endogenous inhibitor of angiogenesis both in vitro and in vivo.lt has been implicated in the regulation of cell growth and proliferation,cell motility,cytoskeletal organization,inflammamtion and wound healing.and the development and differentiation of cell types.COX-2 is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. COX-2 is inducible by a variety of factors, including cytokines, growth factors, and tumor promoters and was initially identified as one of growth response gene, which affect a number of signal transduction pathways that modulate cellular, adhesion, proliferation, apoptosis, and differentiation.It is well known that VEGF, TSP-1, and COX-2 are associated with development of tumor and tumors angiogenesis , however, improved knowledge of the molecularmechanisms hi this disease will be required.Here, we have investigated the expressions and relationship of VEGF, TSP-1 and COX-2 hi BTCC and human bladder cancer cell T24, using in situ hybridization and immunohistochemistry methods. We also identified VEGF, TSP-1 and COX-2 as aprimary factor contributing to the angiogenesis during the development of bladder cancer.Purpose:We investigate the role of VEGF expression, TSP-1 and COX-2mRNA expression in BTCC and human bladder cancer T24 cells; we also identify the relationship between VEGF, TSP-1 and COX-2 expression and tumor angiogenesis. Methods:1. 48 BTCC and 10 normal bladder mucosas were used to detect the expressions of VEGF, TSP-1 and COX-2 by using in situ hybridization and immunchistochemistry, microvessel density counts were also determined.2. cell study:1) For cell viability assays, T24 cells incubated with or without increasing concentration of celecoxib for 4 hour; For the time course experiments, cell were incubated with or without 5 y. M celecoxib and harvested at various time points, After that, cells were stained with trypan blue, and the number of living cells was determined by counting in a hemacytometer.2) Cells were incubated with or without 5 u M celecoxib for 24 hours then detect the expressions of VEGF, TSP-1 and COX-2.Results:1. MVD counts were closely related to tumor grade and clinical stage, MVD counts that in well differentiated, superficial or nonrecurring BTCCs was lower than that in poorly differentiated, invasive or recurring BTCCs (PO.05).2. The level of VEGF expression in BTCCs was higher than that in normal bladder mucosas (P=0.002), the expressions of VEGFin invasive BTCCs was significantly higher compared with superficial BTCCs (P=0.010), but not related to the pathological grade of the tumor (P>0.05), the expression of VEGF in recur...
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