Literature DB >> 19096229

Expression of angiogenesis-related genes regulates different steps in the process of tumor growth and metastasis in human urothelial cell carcinoma of the urinary bladder.

M Chikazawa1, K Inoue, S Fukata, T Karashima, T Shuin.   

Abstract

OBJECTIVE: This study was designed to determine the relative activity of angiogenesis-related genes in the regulation of tumorigenicity and subsequent metastases of urothelial cell carcinomas (UC) of the urinary bladder.
METHODS: We selected the clones with the highest and lowest expression level of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF)/vascular permeability factor or interleukin-8 (IL-8) in the highly tumorigenic and metastatic human UC cell line 253J B-V. Tumorigenicity and production of spontaneous lymph node metastases were evaluated 1, 2, 4, 8 and 12 weeks after orthotopic implantation of each specific expression clone into the urinary bladder of athymic nude mice. Moreover, the transitional changes in the expression of angiogenesis-related genes and neovascularization were determined in tumors and metastases.
RESULTS: At the early stage of tumor growth following orthotopic implantation, tumorigenicity and metastases were significantly increased in the clones with the highest expression of bFGF and IL-8, while they were significantly inhibited in the clones with the lowest expression of bFGF and IL-8 compared to parental 253J B-V. In the tumors, specific expression of angiogenesis-related genes and intratumor neovascularity of each clone were gradually regulated to the same level as parental 253J B-V. In metastasized tumors of the highest and lowest IL-8-expressing clones, IL-8 expression was consistently high and low, respectively.
CONCLUSIONS: These findings indicate that at the early stage of tumor growth, bFGF and IL-8 expression play important roles in the regulation of angiogenesis, tumorigenicity and subsequent metastases of human bladder cancer. Copyright 2008 S. Karger AG, Basel.

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Year:  2008        PMID: 19096229     DOI: 10.1159/000164218

Source DB:  PubMed          Journal:  Pathobiology        ISSN: 1015-2008            Impact factor:   4.342


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