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Recruited T cells promote the bladder cancer metastasis via up-regulation of the estrogen receptor β/IL-1/c-MET signals

Authors :
Chawnshang Chang
Jianxin Qiu
Shuyuan Yeh
Li Zuo
Zhihong Liu
Elizabeth A. Guancial
Spencer Slavin
Zhenyu Ou
Jifu Ge
Edward M. Messing
Le Tao
Source :
Cancer letters. 430
Publication Year :
2017

Abstract

Clinical data indicates that T cells can be recruited to bladder cancer (BCa), yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4+ T cells than did normal bladder cells. The recruiting of T cells to BCa tissues may increase the proliferation and invasion of BCa cells. Mechanistic studies revealed that infiltrating T cells stimulate BCa estrogen receptor beta (ERβ) signaling and consequently increase the expression of MET proto-oncogene, receptor tyrosine kinase (c-MET), through either direct binding to its promoter or via modulation of IL-1 expression. Interruption of ERβ/c-MET or ERβ/IL-1/c-MET signaling via ERβ-shRNA, IL-1 antagonist, or the c-MET inhibitor, SU11274, could partially reverse the T cell-enhanced BCa cell invasion and proliferation. Finally, the mouse BCa model with xenografted BCa 5637 cells with T (HH) cells confirmed the results of in vitro co-culture studies showing that infiltrating T cells could promote BCa metastasis via modulation of the ERβ/c-MET or ERβ/IL-1/c-MET signaling pathways. These findings may provide a new therapeutic approach to better combat BCa progression via targeting these newly identified signaling pathways.

Details

ISSN :
18727980
Volume :
430
Database :
OpenAIRE
Journal :
Cancer letters
Accession number :
edsair.doi.dedup.....06a1f4df35f9e0e44e48c62add67b860