title: Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation.
abstract: Infiltrated macrophages may play important roles in the development and progression of benign prostatic hyperplasia (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 androgen receptor (AR) could enhance the migration of macrophages and macrophage-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.
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Wang
authors.forename: Wen-Jye
authors.initials: WJ
authors.lastname: Lin
authors.forename: Kouji
authors.initials: K
authors.lastname: Izumi
authors.forename: Qi
authors.initials: Q
authors.lastname: Jiang
authors.forename: Kuo-Pao
authors.initials: KP
authors.lastname: Lai
authors.forename: Defeng
authors.initials: D
authors.lastname: Xu
authors.forename: Lei-Ya
authors.initials: LY
authors.lastname: Fang
authors.forename: Tianjing
authors.initials: T
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Shujie
authors.initials: S
authors.lastname: Xia
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D011467:Prostate / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000473:pathology* / Q000503:physiopathology; D011944:Receptors, Androgen / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology*
chemical_list: D017931:DNA Primers; D011944:Receptors, Androgen