A FETAL-RAT UROGENITAL SINUS MESENCHYMAL CELL-LINE (RUGM) - ACCELERATED-GROWTH AND CONFERRAL OF ANDROGEN-INDUCED GROWTH RESPONSIVENESS UPONA HUMAN BLADDER-CANCER EPITHELIAL-CELL LINE IN-VIVO

A cell-cell interaction model was developed to examine the intercellul ar communication between mesenchymal and epithelial cells in vivo, and to define the role of androgen and paracrine growth factors in promot ing growth and differentiation of the target epithelial cells. Uusing this model system, we have demonstrated that, in the presence of andro genic steroids, a fetal urogenital sinus mesenchymal cell line exhibit ed androgen-induced growth responses which resulted in an induction of growth of a non-androgen target epithelial cell line derived from hum an urinary bladder. Our results show that: (1) a rat fetal urogenital sinus mesenchyme-derived cell line (rUGM) accelerated growth and confe rred androgen-induced growth responsiveness upon a non-androgen target cell line, WH, derived from a human bladder transitional-cell carcino ma (TCC); this induction of epithelial tumor growth in vivo occurred i n a fibroblast-specific manner; (2) live fetal rUGM cells are required to promote WH tumor growth in vivo, which suggests that continuous pr oduction of factors that may serve as mediators for paracrine/autocrin e pathways are responsible for androgen stimulation of WH tumor growth in vivo; and (3) although WH tumor growth, mediated by the presence o f rUGM cells, was markedly accelerated by the presence of androgen in vivo, androgen and rUGM cells failed to promote the expression of a hu man prostate-specific antigen (PSA) by WH tumors in vivo. Our results emphasize the importance of organ-specific fibroblasts that promote tu mor growth and mediate androgen-induced growth responses; the accelera ted growth of the bladder epithelium was not accompanied by the expres sion of PSA, a known differentiated gene product produced by human pro static epithelial cells. This report also discusses the potential sign ificance of mesenchymal-epithelial cellular interaction which mediates androgen action and may play an important role by influencing human p rostate tumor growth, progression and differentiation. (C) 1994 Wiley- Liss, Inc.