Neutralizing VEGF bioactivity with a soluble chimeric VEGF-receptor protein flt(1-3)IgG inhibits testosterone-stimulated prostate growth in castrated mice

被引:38
作者
Lissbrant, IF
Hammarsten, P
Lissbrant, E
Ferrara, N
Rudolfsson, SH
Bergh, A [1 ]
机构
[1] Umea Univ, Dept Med Biosci, S-90187 Umea, Sweden
[2] Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA
关键词
angiogenesis; apoptosis; androgen receptor; ventral prostate; endothelial cell; cell proliferation; stereology;
D O I
10.1002/pros.10312
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND. Recent studies show that testosterone-stimulated growth of the glandular tissue in the ventral prostate in adult castrated rats is preceded by increased epithelial VEGF synthesis, endothelial cell proliferation, vascular growth, and increased blood flow. These observations suggest that testosterone-stimulated prostate growth could be angiogenesis dependent, and that VEGF could play a central role in this process. METHODS. Adult male mice were castrated and after 1 week treated with testosterone and vehicle, or with testosterone and a soluble chimeric VEGF-receptor flt(1-3)IgG protein. RESULTS. Treatment with testosterone markedly increased endothelial cell proliferation, vascular volume, and organ weight in the ventral prostate lobe in the vehicle groups, but these responses were inhibited but not fully prevented by anti-VEGF treatment. The testosterone-stimulated increase in epithelial cell proliferation was unaffected by flt(1-3)IgG, but endothelial and epithelial cell apoptosis were increased in the anti-VEGF compared to the vehicle-treated groups. CONCLUSIONS. This study suggests that testosterone stimulates vascular growth in the ventral prostate lobe indirectly by increasing epithelial VEGF synthesis and that this is a necessary component in testosterone-stimulated prostate growth. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:57 / 65
页数:9
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