title: Infiltrating mast cells enhance prostate cancer invasion via altering LncRNA-HOTAIR/PRC2-androgen receptor (AR)-MMP9 signals and increased stem/progenitor cell population.
abstract: Early studies indicated that selective inflammatory immune cells in the prostate tumor microenvironment might be able to influence prostate cancer (PCa) progression. Here we found treating PCa cells with androgen deprivation therapy (ADT) results in the recruitment of more mast cells, which might then increase PCa cell invasion via down-regulation of AR signals in 4 different PCa cell lines. Mechanism dissection revealed infiltrating mast cells could decrease AR transcription via modulation of the PRC2 complex with LncRNA-HOTAIR at the AR 5' promoter region in PCa cells. The consequences of suppressing AR may then increase PCa cell invasion via increased MMP9 expression and/or increased stem/progenitor cell population. The in vivo mouse model with orthotopically xenografted PCa CWR22Rv1 cells with/without mast cells also confirmed that infiltrating mast cells could increase PCa cell invasion via suppression of AR signals. Together, our results provide a new mechanism for the ADT-enhanced PCa metastasis via altering the infiltrating mast cells to modulate PCa AR-MMP9 signals and/or AR-stem/progenitor cell population. Targeting these newly identified inflammatory mast cells-AR signals may help us to better suppress PCa metastasis at the castration resistant stage.
authors.affiliation: Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dang
authors.affiliation: Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.|Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Song
authors.affiliation: Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.affiliation: Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA.|Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001549:Benzamides; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: C410798:AR protein, human; D000813:Anilides; D001549:Benzamides; C561566:HOTAIR long untranslated RNA, human; D009570:Nitriles; D062085:RNA, Long Noncoding; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D010669:Phenylthiohydantoin; C540278:enzalutamide; C053541:bicalutamide; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: HOTAIR-PRC2; androgen receptor; mast cells; prostate cancer; stem cells