title: Androgen receptor facilitates the recruitment of macrophages in tumor microenvironment to promote upper urinary tract urothelial cell carcinoma progression.
abstract: Interactions between infiltrating macrophages in the tumor microenvironment (TME) and tumor cells contribute to tumor progression. The potential impacts of recruited macrophages to the upper urinary tract urothelial cell carcinomas (UUTUCs) progression remain unclear. Here we found human UUTUCs might recruit more macrophages than surrounding normal urothelial cells in human clinical specimens and inin vitroco-culture experiments with UUTUC cells and macrophages. The consequences of recruiting more macrophages to UUTUCs might then enhance UUTUC cell growth, migration and invasion. Further investigation found that the androgen receptor (AR) not only enhanced UUTUC cells capacity to recruit more macrophages, it could also promote the macrophages-enhanced UUTUC cells growth, migration and invasion. Downstream AR target cytokine search found AR might function through modulating CCL5 expression to influence UTTUC progression. Interruption of CCL5 partially reversed the AR-regulated macrophage-enhanced UUTUC progression. AR in UUTUC cells also increased tumor formationin vivo. Taken together, these results suggest that macrophages recruitment may enhance UUTUC progression, modulated by AR-CCL5 signal through alterations in chromatin state to establish a tumor microenvironment with recruited macrophages and cytokines to facilitate cell growth, migration and invasion.
authors.affiliation: Sex Hormone Research Center, Departments of Medical Laboratory Science and Biotechnology and Urology, Graduate Institute of Clinical Medical Science, China Medical University/HospitalTaichung 404, Taiwan; Department of Urology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationTaichung, Taiwan.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Sex Hormone Research Center, Departments of Medical Laboratory Science and Biotechnology and Urology, Graduate Institute of Clinical Medical Science, China Medical University/Hospital Taichung 404, Taiwan.
authors.forename: Chi-Ping
authors.initials: CP
authors.lastname: Huang
authors.affiliation: Department of Urology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Taichung, Taiwan.
authors.forename: Teng-Fu
authors.initials: TF
authors.lastname: Hsieh
authors.affiliation: Sex Hormone Research Center, Departments of Medical Laboratory Science and Biotechnology and Urology, Graduate Institute of Clinical Medical Science, China Medical University/Hospital Taichung 404, Taiwan.
authors.forename: Wei-Kai
authors.initials: WK
authors.lastname: Chiu
authors.affiliation: Sex Hormone Research Center, Departments of Medical Laboratory Science and Biotechnology and Urology, Graduate Institute of Clinical Medical Science, China Medical University/Hospital Taichung 404, Taiwan.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Chang
authors.affiliation: Sex Hormone Research Center, Departments of Medical Laboratory Science and Biotechnology and Urology, Graduate Institute of Clinical Medical Science, China Medical University/Hospital Taichung 404, Taiwan.
authors.forename: Chih-Rong
authors.initials: CR
authors.lastname: Shyr
keywords: Androgen receptor; macrophage; tumor microenvironment; upper urinary tract urothelial cell carcinoma