Transforming growth factor ? in the human prostate: Its role in stromal-epithelial interactions in non-cancerous cell culture

Abstract

BACKGROUND Stromal–epithelial interactions play a critical role in prostate development, but the precise mechanisms are still unknown. Transforming growth factor‐beta (TGFβ) could be a potential mediator of these interactions, but there is as yet no clear demonstration of its role. METHODS Separate cultures and co‐cultures of fibroblasts and epithelial human prostate cells were performed. We measured TGFβ1 and TGFβ2 secretion by specific ELISA assay, cell growth by DNA assay, and TGFβ type II receptor expression by RT‐PCR. RESULTS Co‐culture resulted in a 20% inhibition of epithelial cell growth, similar to that obtained after TGFβ treatment (2 ng/ml for 48 hr), but without affecting fibroblast proliferation. This was accompanied by a five‐ to six‐fold increase in epithelial TGFβ2 secretion. CONCLUSIONS These results demonstrate for the first time that TGFβ2 secretion by prostate epithelial cells is under the direct control of a diffusible factor secreted by fibroblasts. They emphasize the role of TGFβ in stromal–epithelial interactions. Prostate 46:311–318, 2001. © 2001 Wiley‐Liss, Inc.

Stroma Regulates Increased Epithelial Lateral Cell Adhesion in 3D Culture: A Role for Actin/Cadherin Dynamics

“…Active TGFβ2 secretion was increased approximately 2-fold greater (165 pg/ml) than the sum of TGFβ2 secretions measured in the medium of either cell type cultured alone (stroma, 62 pg/ml; acini, 26 pg/ml). A similar change has been found in monolayer culture [27]. Secreted levels of CXCL12 were low in stroma (20 pg/ml) and acini (11 pg/ml) cultured alone, but comparable to published data [21].…”

Proteomic Profiling of Androgen-independent Prostate Cancer Cell Lines Reveals a Role for Protein S during the Development of High Grade and Castration-resistant Prostate Cancer

“…In total, we identified a 3110-non-redundant protein data set, which, to our knowledge, is the most comprehensive one to date. To internally validate our approach, we observed among our top candidates, 12 proteins (MGAT5, PAM, GBA, ROBO1, CD59, MMP1, IGFBP4, CDH2, TGFB2, ICAM1, EPHA2, and IGFBP5) that have previously been studied or implicated in prostate cancer progression (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). For example, MGAT5 has been shown to mediate enhanced invasion and metastatic potential for prostate cancer cells through many in vitro invasion assays and xenograft animal models.…”

In silicodissection of cell-type-associated patterns of gene expression in prostate cancer

“…Transcripts with high cross-products in the covariance matrix suggest that expression in one cell type was not independent of the proportion of another tissue, as would be expected in a paracrine mechanism. The stroma transcript with the highest dependence on tumor percentage was TGF-␤2, a cytokine previously identified as important in prostate cell proliferation (19). Another such stroma cell gene for which immunohistochemistry was practical was desmin, which showed considerably altered staining in the tumor-associated stroma.…”