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.
Qi Jiang Bang-Min Han Fu-Jun Zhao Yan Hong Shu-Jie Xia
This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone(TZ)or peripheral zone(PZ)in the carcinogenesis of prostate cancer(PCa)epithelial cells(PC-3)in vitro and in vivo co-culture models.Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis.In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established.We assessed tumor growth and weight in the in vivo nude mice model.There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate.In all,514 differentially expressed genes were selected by microarray analysis;483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ.Co-culture with PZ stromal cells and transforming growth factor-β1(TGF-β1)increased the tumor growth of PC-3 cells in vitro and in vivo,as well as Bcl-2 expression.On the other hand,stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model.We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate,and stroma-epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation.
