Differential effects of transforming growth factor β on human prostate cancer cells in vitro

Transforming growth factor β (TGFβ) exerts a wide spectrum of activity on many different cell types. Since TGFβ inhibits the growth of a variety of epithelial tumor cells in vitro, we examined the effects of TGFβ on the human prostate cancer cell lines DU145, PCS and LNCaP for possible inhibitory activity. Growth in monolayer was initially inhibited in a dose-response fashion in the two androgen-independent cell lines, PC3 and DU145 but not in the androgen-dependent LNCaP cells. The rate of growth of the PC3 and DU145 cells treated with TGFβ, however, eventually returned to control levels despite retreatment with TGFβ. Anchorage-independent growth was inhibited to 55% and 16% control levels in PC3 and DU145, respectively. Scatchard analysis showed 1500 and 2900 TGFβ binding sites/cell on DU145 and PC3 cells with K_d = 6.9 and 12 × 10^-12 M, respectively. High-affinity binding could not be demonstrated on LNCaP cells. We also explored the possibility that TGFβ was secreted by these cells. Analysis of conditioned media by immunoprecipitation and a radioreceptor assay showed secretion of TGFβ into the media by DU145 and PC3 but not by LNCaP. Northern analysis showed the presence of TGFβ mRNA in DU145 and PC3, but not in LNCaP. These data indicate that TGFβ might serve as an autocrine inhibitory factor in prostate cancer. In addition, because TGFβ affects a wide range of cell types, TGFβ production by prostate cancer cells may contribute an important paracrine function in the development of tumor stromal tissue and metastases.