The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

• Published in: Asian journal of andrology Vol. 13; no. 6; pp. 798 - 805
• Main Authors: Jiang, Qi, Han, Bang-Min, Zhao, Fu-Jun, Hong, Yan, Xia, Shu-Jie
• Format: Journal Article
• Language: English
• Published: China Medknow Publications & Media Pvt. Ltd 01.11.2011; Nature Publishing Group
• Subjects: Androgen receptors; Base Sequence; Benign; Blotting, Western; Cell Proliferation; Coculture Techniques; Data processing; Development; Dihydrotestosterone; DNA Primers; Enzyme-Linked Immunosorbent Assay; Epithelial cells; Gonadal Steroid Hormones - genetics; Gonadal Steroid Hormones - physiology; Growth Substances - physiology; Humans; Hyperplasia; Insulin-like growth factor I; Keratinocyte growth factor; Male; mRNA; Original; peptide growth factors; Polymerase chain reaction; Proliferating Cell Nuclear Antigen - metabolism; Prostate; Prostate - cytology; Prostate cancer; Prostatic Neoplasms - pathology; Prostatic Neoplasms - physiopathology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Real-Time Polymerase Chain Reaction; Secretion; Sex hormones; stromal cells; Stromal Cells - cytology; Transforming growth factor- beta 1; Western blotting; 上皮细胞; 前列腺癌; 基质细胞; 性激素; 细胞治疗; 胰岛素样生长因子-1; 良性前列腺增生; 角质细胞生长因子
• ISSN: 1008-682X; 1745-7262
• DOI: 10.1038/aja.2011.22

It is well known that prostate cancer （PCa） occurs predominantly in the peripheral zone （PZ）, whereas benign prostatic hyperplasia （BPH） typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone （PZsc） and the transition zone （TZsc） on a PCa epithelial cell line （PC3） in the presence of sex hormones. First, we observed that androgen receptor （AR） mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone （DHT） and β-oestradiol （E2） （P〈0.05）. By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor （KGF） secretion increased with increasing concentrations of DHT （P〉0.01） and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-β1 （TGF-β1） than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 （IGF-1） secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmoll^- 1 DHT plus 10 nmoll^-1 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.