| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Research Abstract |
Purpose : This study was designed to determine the relative activity of basic fibroblast growth factor (bFGF), vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), and interleukin-8 (IL-8) in the process of regulating tumorigenicity and metastasis of transitional cell carcinoma (TCC) of the urinary bladder.
Experimental Design : We selected the specific expression clones as indicated to the expression level of bFGF, VEGF or IL-8 m highly tumorigenic and highly metastatic human TCC cell line 253JB-V. We evaluated transitionally tumorigemcily and production of spontanous lymph node metastases after orthotopic implantation of the specific expression clones. To assess the transitional changes of angiogenesis and the expression of angiogenic factors, intratumor neovascularization and mRNA expression of angiogenic factors were determined in the tumors.
Results : In vitro, the highest and lowest specific expression clones demonstrated stable expression of specific total R
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NA and protein. Following implantation into the bladders of athymic nude mice, the highest bFGF- and the highest IL-8-expressing clone cells acquired increased tumorigenicity in only early stage. Moreover, the tumorigenicity of the lowest bFGF- and the lowest IL-8-expressing clone were consistently inhibited through all stages compared to parental 253JB-V cell lines. The highest bFGF- and the highest IL-8-expressing clone cells relatively acquired matastasis in earlier stage. Moreover, the metastasis of the lowest IL-8-expressing clone was relatively inhibited compared to parental 253JB-V cell lines. However, the tumorigenicity and metastasis of the specific expression clones of VEGF were not significantly different from that of parental 253JB-V cell lines.
In the tumors, each highest expressing clone significantly increased the specific mRNA expression and neovascularity, and each lowest expressing clone significantly decreased specific mRNA expression and neovascularity in only early stage compared to parental 253JB-V cell lines. However, the intratumor neovascularity and the expression level or bFGF, VEGF and IL-8 in the tumor of the specific expression clones were gradually regulated to the same expression level as parental 253JB-V cell lines within 4 weeks.
Conclusions : These findings indicate that the expression of bFGF regulates angiogenesis, tumorigenicity especially in early stage of tumor progression of human TCC growing in the urinary bladder of athymic nude mice. Thereore, this study provided tha evidence that the therapy targeting angiogenesis pathways such as bFGF represents a novel, effective, and promising therapy with significant anti-tumoral effect, in the early stage of tumor progression of TCC in the urinary bladder. Less
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