Inhibition of prostatic epithelial cell proliferation by a factor secreted specifically by prostatic stromal cells

Abstract

Stromal cells from the prostate were recently shown to inhibit clonal growth of the prostatic carcinoma cell lines PC-3 (hormone-independent) and LNCaP (hormone-sensitive) in coculture. Our study revealed that stromal cell-conditioned medium strongly inhibited proliferation of PC-3 and LNCaP cells when grown in monolayer culture. Antiproliferative activity was found to be reversible, and was produced specifically by prostatic stromal cells and not by stromal cells derived from skin, foreskin, uterus, kidney, and Wilms' tumor. Inhibition was not species-specific, since the cell lines AT-2.1 and MATLyLu, derived from the Dunning rat prostate tumor, were also sensitive. No inhibition, however, occurred on breast and renal carcinoma cell lines, suggesting a prostate-specific action. The putative inhibiting factor(s) could be concentrated and partially purified by ammonium sulfate precipitation. The possible role in stromal control of epithelial cell proliferation is discussed.

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

“…Although a serum-free environment is ideal for testing as well as identification of regulatory peptides, certain information may be lost, as suggested by the findings reported by Kirk et al (1981) and Rowley (1992b), and the results presented here. The prostatic stromal cell-derived antiproliferative activity we found was mediated by a diffusible factor present in serumcontaining conditioned medium (CM) of stromal cells from neoplastic lesions of (adult) prostates (Konig et al, 1987;Kooistra et al, 1991Kooistra et al, , 1995a. In the present report we show that this factor is different from TGF-P, its related peptides inhibin and activin, and from other inhibitors previously described.…”

“…(Vogel, Giessen, Germany). Using this 'first-step' purification procedure, 75% of contaminating protein could be discarded (Kooistra et al, 1995a).…”

Inhibition of Epithelial Ductal Branching in the Prostate by Sonic Hedgehog Is Indirectly Mediated by Stromal Cells

“…Consistent with this notion, conditioned media collected from primary stromal cell cultures inhibit prostatic epithelial cell proliferation (52). Activin A (38,39) and TGF-␤1 (40) have been shown to exert inhibitory effects on epithelial cell growth and branching morphogenesis and are found to be expressed in the prostatic stromal cells.…”

“…Tissue recombination studies show that urogenital sinus mesenchymal cells can induce epithelial cells from non-prostatic tissues to become prostatic epithelial cells (42,70), and such induction is determined by the amount of mesenchymal tissue present (71,72). Stromaepithelial cell co-culture experiments also indicate that although carcinoma-associated stromal cells enhances prostatic carcinogenesis (72,73), normal stromal cells are capable of inhibiting prostatic carcinogenesis by inducing differentiation and inhibiting the proliferation of the epithelium (52,74,75). Consistent with this notion, a reduction in the number of normal stromal smooth muscle cells is closely associated with progression of prostatic carcinogenesis (76).…”

Models for studying benign prostatic hyperplasia

“…22 In general, techniques for primary human cell culture require either multicomponent media 23,24 or extensive periods of digestion. 25 The base media commonly contained cholera toxin, bovine pituitary extract, retinoic acid and insulin. Pituitary extract contains many hormones and growth factors.…”