Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): the role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation
Wang X, Lin WJ, Izumi K, Jiang Q, Lai KP, Xu D, Fang LY, Lu T, Li L, Xia S, Chang C. J Biol Chem. 2012 Apr 2. [Epub ahead of print]


University of Rochester, United States;


Infiltrated macrophages may play important roles in the development and progression of BPH, but the underlying mechanisms remain largely unknown. We found increased macrophages infiltration in human and mouse BPH tissues. By establishing a co-culture transwell system, we found increased migration of macrophages and proliferation of prostate stromal cells during co-culture. Importantly, stromal AR could enhance the migration of macrophages and the macrophages-mediated stromal cell proliferation. We identified CCL3 as an AR downstream player, and found CCL3 levels were notably increased in human and mouse BPH prostates. Ablation of prostate stromal AR in a mouse BPH model significantly reduced CCL3 expression levels in prostates. Consistently, targeting AR via an AR degradation enhancer, ASC-J9, or neutralization of CCL3 with an antibody, resulted in suppression of macrophage migration and prostate stromal cell growth. Our study provides mechanistic insights on the regulation of prostate stromal cells by macrophages via stromal AR/CCL3 signaling pathways, which could potentially allow the development of therapeutic approaches for battling BPH with persistent inflammation.