Hepatocyte growth factor secreted by prostate-derived stromal cells stimulates growth of androgen-independent human prostatic carcinoma cells

The objective of the present study is to examine the role of prostate stromal cells on growth and progression of prostate cancer. Go-inoculation of androgen-independent carcinoma cells (PC-3 and GA-7T2) with prostate-derived stromal (P-ST) cells significantly enhanced the growth of carcinoma cells in athymic nude mice. For the in vitro study, a three-dimensional co-culture system was used. It consisted of two layers of collagen gel. Stromal cells were suspended in the lower layer, whereas cancer cells were suspended in the upper layer. Compared to the control culture, the presence of P-ST cells in the lower collagen layer significantly stimulated the growth of carcinoma cells. Such an effect was not demonstrated when carcinoma cells were co-cultured with either bone marrow-derived or skin-derived stromal cells. We identified hepatocyte growth factor (HGF) as the principal growth factor released by P-ST cells but not by bone marrow-derived or skin-derived stromal cells. Neutralizing antibodies against HGF completely abrogated the stimulatory effect of P-ST cells. Exogenous HGF likewise stimulated the growth of carcinoma cells in vitro and in vivo. These results suggest that HGF produced by P-ST cells is a paracrine growth factor that stimulates the growth of androgen-independent prostate cancer cell lines.