Vascular endothelial growth factor content in metastasizing and nonmetastasizing dunning prostatic adenocarcinoma

BACKGROUND. Tumor angiogenesis is important in progressive tumor growth and metastasis. In the normal rat prostate and in androgen-sensitive prostate tumors androgen ablation causes an involution of the vasculature and a decr ease in the vascular endothelial growth factor (VEGF) levels before regress ion of the prostate gland. To examine whether angiogenesis and metastasis a re regulated by VEGF in androgen-insensitive and metastasizing prostate tum ors, five Dunning rat prostate cancer sublines were tested; the androgen-se nsitive, nonmetastasizing R3327 PAP, and the androgen-insensitive, low meta stasizing AT-1, and the three androgen-insensitive, metastasizing AT-2, AT- 3, and MatLyLu Dunning prostatic adenocarcinomas. METHODS. VEGF levels were quantified in the rat dorsolateral prostate and i n the five Dunning sublines using competitive RT-PCR, Western blot, and Eli sa. Vascular density was determined by factor VIII staining. RESULTS. VEGF mRNA was increased in all tumors compared with normal prostat es. The two metastatic sublines AT-3 and MatLyLu and the nonmetastatic subl ine AT-1 showed the highest VEGF mRNA expression. VEGF protein levels in th e prostate gland showed increased expression in the metastatic sublines, AT -2, AT-3, and MatLyLu, compared with the nonmetastatic AT-1 subline and the ventral prostate. VEGF proteins in serum were highest in the metastatic AT -3 subline. The vessel density was highest in the two highly metastatic sub lines AT-3 and MatLyLu. CONCLUSIONS. Our results suggest that VEGF levels are associated with micro vessel density and the previously established metastatic pattern of these r at prostate tumor systems. (C) 2000 Wiley-Liss, Inc.