We previously demonstrated that angiotensin II (Ang-II) activated the proliferation of prostate cancer cells, and that Ang-II receptor blockers (ARB) could inhibit it. In the present study we investigated whether Ang-II exerts mitogenic effects on the cross-talk between stromal and cancer cells, and whether an ARB can inhibit tumor growth through actions on stromal cells. [Materials and Methods] Cell proliferation and IL-6 secretion of prostate stromal PrSC cells were examined when these cells were stimulated with Ang-II, TNFα or EGF in the absence and presence of ARB. Further, we examined the effect of ARB on MAPK phosphorylation of PrSC cells and of PC-3 cells treated with conditioned medium (CM) of PrSC cells, and determined the effect of ARB on tumor growth induced by paracrine factors from PrSC cells. [Results] Ang-II activated the cell proliferation and IL-6 secretion of PrSC cells, and ARB inhibited it. Ang-II, TNFα or EGF induced MAPK and STAT3 phosphorylation in PrSC cells, and this phosphorylation was inhibited by ARB. CM of PrSC cells with Ang-II activated MAPK phosphorylation in PC-3 cells, and ARB-treated CM of PrSC cells inhibited it. The tumor growth and angiogenesis of a mixture of PC-3 with PrSC were inhibited by ARB administration, while those of PC-3 xenografts were not inhibited. [Discussion] It is well known that prostatic stromal cells, especially fibroblasts, are involved in the development of hormone-refractory prostate cancer accompanied by the secretion of several growth factors. We confirmed that Ang-II augmented the secretion of IL-6 and another cytokines from prostatic stromal cells and ARB inhibited it. ARB exerted an antiproliferative effect on prostate cancer through paracrine factors from stromal cells. Because prostate stromal cells are thought to be involved in the initiation and development of prostate cancer, the present data suggest the possibility that ARBs are a novel therapeutic class of agents for prostate cancer.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]