Infiltrating neutrophils increase bladder cancer cell invasion via modulation of androgen receptor (AR)/MMP13 signals
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ChangYi Lin1,*, WanYing Lin1,*, Shuyuan Yeh1, Lei Li1,2, Chawnshang Chang1,3
1George Whipple Lab for Cancer Research, Departments of Pathology and Urology, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester 14642, New York, USA
2Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
3Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan
*These authors have contributed equally to this work
Lei Li, e-mail: [email protected]
Chawnshang Chang, e-mail: [email protected]
Keywords: bladder cancer, neutrophil, microenvironment, androgen receptor
Received: April 14, 2015 Accepted: October 06, 2015 Published: October 16, 2015
Early studies indicated that several inflammatory immune cells, including macrophages, mast cells, B and T cells in the tumor microenvironment, might influence cancer progression. Here we found that bladder cancer (BCa) cells could recruit more neutrophils than normal bladder cells. The consequences of recruiting more neutrophils might then increase BCa cell invasion via up-regulating androgen receptor (AR) signals. Mechanism dissection revealed infiltrating neutrophils could up-regulate AR signals via either increased AR mRNA/protein expression or increased AR transactivation. The increased AR signals might then enhance BCa cell invasion via increasing MMP13 expression. Together, these results might provide us a new potential therapeutic approach to better battle BCa metastasis via targeting the newly identified signaling from infiltrating neutrophils to BCa through AR to MMP13 signals.
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