Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo

The Prostate
P BorgströmN Ferrara

Abstract

Neovascularization mediated by growth factors produced by tumors is critical for the growth of tumors. Vascular endothelial growth factor (VEGF) is one such growth factor. A neutralizing anti-VEGF antibody (A4.6.1) was recently shown in vivo to inhibit tumor angiogenesis and growth of the human rhabdomyosarcoma cell line A673. The antibody profoundly changed the growth characteristics of the tumor line from a rapidly growing malignancy to a dormant microcolony. In the present study, we evaluated the effects of A4.6.1 (100 microg twice weekly, i.p.) on growth and angiogenic activity of spheroids of the human prostatic cell line DU 145 (diameter 700 microm at implantation) implanted in dorsal skinfold chambers in nude mice (n = 11). An antibody of the same isotype (n = 5) or saline (n = 5) was used as control. Tumor cells were prelabeled with a fluorescent vital dye (CMTMR), which allowed measurement of size of the implanted tumor spheroids throughout a two week observation period. FITC-dextran was used for plasma enhancement to visualize angiogenic activity. Tumors of control animals induced a neo-vasculature with high vascular density (350+/-12 cm[-1]). In animals treated with the anti-VEGF antibody, there was complete inhibiti...Continue Reading

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