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 strom al cells on growth and progression of prostate cancer. Go-inoculation of an drogen-independent carcinoma cells (PC-3 and GA-7T2) with prostate-derived stromal (P-ST) cells significantly enhanced the growth of carcinoma cells i n 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 cell s in the lower collagen layer significantly stimulated the growth of carcin oma 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 r eleased by P-ST cells but not by bone marrow-derived or skin-derived stroma l cells. Neutralizing antibodies against HGF completely abrogated the stimu latory effect of P-ST cells. Exogenous HGF likewise stimulated the growth o f carcinoma cells in vitro and in vivo. These results suggest that HGF prod uced by P-ST cells is a paracrine growth factor that stimulates the growth of androgen-independent prostate cancer cell lines.