BASIC FGF, EGF, AND PDGF MODIFY TGF-BETA-INDUCTION OF SMOOTH-MUSCLE CELL PHENOTYPE IN HUMAN PROSTATIC STROMAL CELLS

BACKGROUND. We investigated the ability of a variety of growth factors to regulate the differentiation of prostatic fibroblasts into smooth muscle cells. METHODS. Smooth muscle actin levels were monitored by im munoblot analysis and immunocytochemistry . Proliferation was measured in clonal growth assays and by cell counts. RESULTS. We determined th at TGF beta inhibited proliferation and induced smooth muscle differen tiation of stromal cells derived from prostatic adenocarcinomas, as we previously reported for cells derived from the normal peripheral zone . Basic FGF, EGF, TGF alpha, and PDGF, but not IGF, retinoic acid, 1,2 5-dihydroxyvitamin D-3, or androgen, attenuated induction of different iation by TGF beta, by a mechanism apparently unrelated to proliferati on. CONCLUSIONS. Regulation of growth and differentiation occurs equiv alently in prostatic stromal cells derived from adenocarcinomas and no rmal peripheral zone. TGF beta is a potent inducer of the smooth muscl e phenotype. Basic FGF, EGF and/or TGF alpha, and PDGF attenuate TGF b eta's activity, and promote a fibroblastic phenotype. Our studies prov ide an in vitro model system in which fibroblastic or smooth muscle ce lls can be promoted, maintained, and investigated in a defined manner. The results suggest that the ratio of fibroblasts to smooth muscle ce lls in the stroma reflects the relative levels of growth factors, whic h may be altered in diseased states. (C) 1998 Wiley-Liss, Inc.