Aging up-regulates ARA55 in stromal cells, inducing androgen-mediated prostate cancer cell proliferation and migration.

Stromal cells in the peripheral zone (PZ) of the prostate from older males (PZ-old) could significantly promote Prostate cancer (PCa) growth compared with stromal cells from young males (PZ-young). But the mechanism is still unknown. In the co-culture system with PZ-old cells, Pc3/Du145 cells showed advanced proliferation and migration after Dihydrotestosterone (DHT) incubation, but DHT didn't show the similar effect in PZ-young co-culture system. Also, higher androgen/AR signal pathway activity and AR-related cytokines secretion (FGF-2, KGF, IGF-1) were found in PZ-old cells. As AR exprssison was equivalent in PZ-old and PZ-young cells, we focused on Androgen receptor associated protein-55(ARA55), a stromal-specific androgen receptor (AR) coactivator. ARA55 expression was higher in PZ-old cells compared with PZ-young cells in vitro. After knocking down ARA55 expression in PZ-old cells, the PCa growth- promoting effect from the PZ-old cells was diminished, which may be explained by the decreased the progressive cytokines secretion (FGF-2, KGF, IGF-1) from PZ-old stromal cells. In vivo, the consistent results were also found: PZ-old cells promoted prostate cancer cells growth, but this effect receded when knocking down ARA55 expression in PZ-old cells. From our study, we found PZ stromal cells presented age-related effects in proliferation and migration of prostate cancer cells in the androgen/AR dependent manner. As aging increased, more ARA55 were expressed in PZ stromal cells, leading to more sensitive androgen/androgen receptor (AR) signal pathway, then constituting a more feasible environment to cancer cells.

Journal of molecular histology. 2016 May 13 [Epub ahead of print]

Qingsong Zou, Di Cui, Shengjie Liang, Shujie Xia, Yifeng Jing, Bangmin Han

Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China., Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China., Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China., Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China., Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China. ., Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China. .