Infiltrating mast cells enhance prostate cancer invasion via altering LncRNA-HOTAIR/PRC2-androgen receptor (AR)-MMP9 signals and increased stem/progenitor cell population
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Lei Li1,2,*, Qiang Dang1,2,*, Hongjun Xie1,2, Zhao Yang1, Dalin He1, Liang Liang1,2, Wenbing Song1,2, Shuyuan Yeh2, Chawnshang Chang2,3
1 Department of Urology, Sex Hormone Research Center, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
2 Departments of Pathology and Urology, George Whipple Lab for Cancer Research, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA
3 Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan
* These authors have contributed equally to this work
Lei Li, email:
Chawnshang Chang, email:
Keywords: prostate cancer, mast cells, androgen receptor, stem cells, HOTAIR-PRC2
Received: November 04, 2014 Accepted: February 28, 2015 Published: March 26, 2015
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.
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