Influences of angiogenic factors affecting growth and progression of the bladder cancer.

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1) Expression of VEGF and its receptor genes in transitional cell carcinoma (TCC) of the bladder.VEGF transcripts and its product were observed in all of the tumors. The VEGF gene expression of invasive TCCs was significantly higher than that of superficial TCCs (p<0.05). All of the tumors as well as the normal mucosae and HUVEC-1 cells expressed flt-1 gene, while WBCs of patients did not. The expression level of flt-1 gene was significantly correlated with that of VEGF gene in the tumor. These results have demonstrated that the VEGF are frequently overexpressed in TCC,especially in muscle invasive tumors, and a paracrine system exists between the TCC cells and the adjacent endothelial cells, regulating the angiogenesis in the TCC.2) Regulation of VEGF gene expression in TCC.Aberrations of p53 gene was detected in 38.7% of urothelial carcinomas and had a tendency to be dominant in high grade and high stage tumors. The VEGF gene expression of muscular invasive urothelial carcinomas was … More higher than those of normal mucosae and superficial tumors (p<0.01). There was, however, no significant difference in VEGF expression between the tumors with p53 gene aberration and the tumors without it. These results suggest that both VEGF and p53 genes play important roles in malignant potential of the urothelial carcinoma. However, VEGF gene expression is regulated by a mechanism other than p53 in this tumor.3) Angiogenic factors and microvessels in TCC.Positive rate of VEGF,bFGF and aFGF were 50%, 23% and 43% in the superficial bladder cancer, respectively. T1 tumors had a higher maximum vessel density than Ta. Microvessels were highlighted by staining for factor VIII-related antigen. Average vessel density and vascular surface density of the tumor were higher than those of normal epithelium. Significant negative correlation between the number of angigenic factors expressed and vessel density was found. These findings suggest that the expression of angiogenic factors correlates with malignant transformation of urothelium, angiogenesis is required topically at the invasive front of the superficial bladder cancer.Summary ; Angiogenic factors, especially VEGF,play important roles in transformation and progression as well as angiogenesis of this tumor Less