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

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...

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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
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Summary:	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.
Bibliography:	androgen; growth factor; oestrogen; prostate cancer; stromal cell 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. 31-1795/R ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	1008-682X 1745-7262
DOI:	10.1038/aja.2011.22