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

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 te...

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Veröffentlicht in:The Prostate 2004-01, Vol.58 (1), p.57-65
Hauptverfasser: Lissbrant, Ingela Franck, Hammarsten, Peter, Lissbrant, Erik, Ferrara, Napoleone, Rudolfsson, Stina Häggström, Bergh, Anders
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Sprache:eng
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Zusammenfassung: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. © 2003 Wiley‐Liss, Inc.
ISSN:0270-4137
1097-0045
DOI:10.1002/pros.10312