Inhibition of vascular endothelial cell growth factor suppresses the in vivo growth of human prostate tumors

The LNCaP human prostate cancer cell line is androgenand stromal-dependent for in vivo growth. We co-inoculated LNCaP cells with human fetal fibroblasts, isolated from prostate, bone (male), and lung (male and female) derived from 18- to 22-week-old human fetal tissue, into non-castrate male nude mice. Co-inoculation of LNCaP with fetal prostatic fibroblasts resulted in high tumor take rates (27 of 30, or 90%) 6 to 8 weeks after subcutaneous co-inoculation. Serum prostate specific antigen (PSA) values correlated strongly with wet tumor weight (r=0.86). The fetal fibroblast enhancement of tumor take rates in vivo was neither gender- nor organ-specific. Fetal fibroblast-conditioned medium (CM) did not have a significant proliferative effect on LNCaP cell growth in vitro. Areas of angiogenesis were demonstrable in all tumors, with blood vessels arising at the interface between stromal and tumor cells. The fetal fibroblasts, but not the LNCaP cells, expressed significant amounts of the mRNA and protein for vascular endothelial cell growth factor (VEGF). Treatment of tumor-bearing animals with neutralizing antibodies to VEGF resulted in significant tumor growth suppression. These findings indicate that VEGF is an important mediator of stromal-induced enhancement of human prostate cancer cell growth in vivo.