INDUCTION OF SMOOTH-MUSCLE CELL PHENOTYPE IN CULTURED HUMAN PROSTATICSTROMAL CELLS

Stromal cells are key regulators of growth and differentiation in the adult human prostate. Alterations in the stroma are believed to initia te the development of benign prostatic hyperplasia, and stromal-epithe lial interactions may have a role in malignant progression. The prosta tic stroma is composed of two major cell types, smooth muscle cells an d fibroblasts. Cell cultures from the prostatic stroma have been estab lished by several investigators, but the phenotype of these cells has not been extensively characterized and it is not clear whether they ar e fibroblastic or smooth muscle-like. In this study, the response of s tromal cells cultured from normal prostatic tissues to transforming gr owth factor-beta (TGF beta) was investigated. We confirmed a previous report that TGF beta inhibited the growth of prostatic stromal cells i n serum-containing medium, and showed that inhibition also occurred in serum-free medium. Growth inhibition by TGF beta was irreversible aft er 24 to 72 h of exposure. In the absence of TGF beta, cells were fibr oblastic and expressed vimentin and fibronectin but little alpha-smoot h muscle actin. After 3 days of exposure to 1 ng/ml of TGF beta, the m ajority of cells expressed alpha-smooth muscle actin and desmin, as de monstrated by immunocytochemistry and immunoblot analysis. This effect was specific and alpha-smooth muscle actin was not induced by two oth er growth-inhibitory factors, retinoic acid or 1,25-dihydroxyvitamin D -3. These results suggest that TGF beta is an important regulator of g rowth and differentiation of prostatic stromal cells and that a smooth muscle cell phenotype is promoted in the presence of TGF beta. (C) 19 97 Academic Press.