A fetal rat urogenital sinus mesenchymal cell line (rUGM): accelerated growth and conferral of androgen-induced growth responsiveness upon a human bladder cancer epithelial cell line in vivo

Abstract

A cell-cell interaction model was developed to examine the intercellular communication between mesenchymal and epithelial cells in vivo, and to define the role of androgen and paracrine growth factors in promoting growth and differentiation of the target epithelial cells. Using this model system, we have demonstrated that, in the presence of androgenic steroids, a fetal urogenital sinus mesenchymal cell line exhibited androgen-induced growth responses which resulted in an induction of growth of a non-androgen target epithelial cell line derived from human urinary bladder. Our results show that: (1) a rat fetal urogenital sinus mesenchyme-derived cell line (rUGM) accelerated growth and conferred androgen-induced growth responsiveness upon a non-androgen target cell line, WH, derived from a human bladder transitional-cell carcinoma (TCC); this induction of epithelial tumor growth in vivo occurred in a fibroblast-specific manner; (2) live fetal rUGM cells are required to promote WH tumor growth in vivo, which suggests that continuous production of factors that may serve as mediators for paracrine/autocrine pathways are responsible for androgen stimulation of WH tumor growth in vivo; and (3) although WH tumor growth, mediated by the presence of rUGM cells, was markedly accelerated by the presence of androgen in vivo, androgen and rUGM cells failed to promote the expression of a human prostate-specific antigen (PSA) by WH tumors in vivo. Our results emphasize the importance of organ-specific fibroblasts that promote tumor growth and mediate androgen-induced growth responses; the accelerated growth of the bladder epithelium was not accompanied by the expression of PSA, a known differentiated gene product produced by human prostatic epithelial cells. This report also discusses the potential significance of mesenchymal-epithelial cellular interaction which mediates androgen action and may play an important role by influencing human prostate tumor growth, progression and differentiation.