Recruited T cells promote the bladder cancer metastasis via up-regulation of the estrogen receptor β/1L-1/c-MET signals
Recruited T cells promote the bladder cancer metastasis via up-regulation of the estrogen receptor β/1L-1/c-MET signals
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招募的 T 细胞通过上调雌激素受体 beta/1L-1/c-MET 信号促进膀胱癌转移
DOI：
10.1016/j.canlet.2018.03.045
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Yeh, Shuyuan
中科院分区：
文献类型：
--
作者：
Tao, Le;Qiu, Jianxin;Yeh, Shuyuan
临床数据表明，T细胞可以被招募到膀胱癌（BCa），但T细胞对BCa进展的影响仍不清楚。在本研究中，我们发现，T细胞募集更多的BCa组织比周围的正常膀胱组织。体外共培养系统的结果还发现，BCa比正常膀胱细胞招募更多的CD 4（+）T细胞。T细胞向BCa组织的募集可增加BCa细胞的增殖和侵袭。机制研究表明，浸润性T细胞刺激BCa雌激素受体β（ER β）信号传导，并因此通过直接结合其启动子或通过调节IL-1表达来增加MET原癌基因受体酪氨酸激酶（c-MET）的表达。通过ER β-shRNA、IL-1拮抗剂或c-MET抑制剂SU 11274阻断ER β/c-MET或ER β/IL-1/c-MET信号传导，可以部分逆转T细胞增强的BCa细胞侵袭和增殖。最后，异种移植BCa 5637细胞与T（HH）细胞的小鼠BCa模型证实了体外共培养研究的结果，表明浸润性T细胞可通过调节ER β/c-MET或ER β/IL-1/c-MET信号传导途径促进BCa转移。这些发现可能提供一种新的治疗方法，通过靶向这些新发现的信号通路来更好地对抗BCa进展。(C)2018爱思唯尔B. V.保留所有权利。
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 (ER beta) 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 ER beta/c-MET or ER beta/IL-1/c-MET signaling via ER beta-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 ER beta/c-MET or ER beta/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. (C) 2018 Elsevier B.V. All rights reserved.