Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role...Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma of the bladder has not beenclearly elucidated. Here, we dissected the effect of VEGFduring bladder tumor growth and progression by modifying a BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine) induced mouse bladder transitional cell carcinoma cell lineBTT-T739 by stable transfection of antisense VEGF121 cDNA. The transfection resulted in more than 80% reduction inVEGF production. The growth of the transduced tumor cells in vitro was not affected, however, these cells formed small or no tumors in vivo. Even in the tumors formed, there were mini- mal vascularization, extensive necrosis and longerlatency compared to those formed by parental cells. Thepermeability of tumor vasculature and metastatic tumor growth were also significantly suppressed in antisense VEGFcDNA trans- fected cells. In addition, the transfer ofanti-angiogenic gene in a combination of sFlk-1 and ExTekwith electroporation can suppress the tumor growthefficiently. Taken together, these results demonstrated thatVEGF plays an important role in bladder tumorangiogenesis and angiogenesis plays an important role in bladder tumor growth and metastasis.展开更多
基金supported by“the Project for Talent Accomplishment”(Health Bureau and Bureau of Human Resource,Shanghai,China)the“Outstanding Scientists”and“White Magnolia”of the Science and Technology Committee of Shanghai Municipality,China.
文摘Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma of the bladder has not beenclearly elucidated. Here, we dissected the effect of VEGFduring bladder tumor growth and progression by modifying a BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine) induced mouse bladder transitional cell carcinoma cell lineBTT-T739 by stable transfection of antisense VEGF121 cDNA. The transfection resulted in more than 80% reduction inVEGF production. The growth of the transduced tumor cells in vitro was not affected, however, these cells formed small or no tumors in vivo. Even in the tumors formed, there were mini- mal vascularization, extensive necrosis and longerlatency compared to those formed by parental cells. Thepermeability of tumor vasculature and metastatic tumor growth were also significantly suppressed in antisense VEGFcDNA trans- fected cells. In addition, the transfer ofanti-angiogenic gene in a combination of sFlk-1 and ExTekwith electroporation can suppress the tumor growthefficiently. Taken together, these results demonstrated thatVEGF plays an important role in bladder tumorangiogenesis and angiogenesis plays an important role in bladder tumor growth and metastasis.
