Role of chemokine receptor CXCR7 in bladder cancer progression
Role of chemokine receptor CXCR7 in bladder cancer progression
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DOI：
10.1016/j.bcp.2012.04.007
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发表时间：
2012-07-15
影响因子：
5.8
通讯作者：
Wang, Jianhua
中科院分区：
文献类型：
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作者：
Hao, Mingang;Zheng, Jianghua;Wang, Jianhua
膀胱癌是泌尿生殖道最常见的肿瘤之一;然而，肿瘤生长和侵袭的分子基础尚不清楚。在此，进一步探讨了CXCR 7受体在膀胱癌中的作用。使用高密度组织芯片检测CXCR 7蛋白表达。CXCR 7的表达显示出与膀胱癌进展相关的强上皮染色。在膀胱癌细胞系中的体外和体内研究表明，CXCR 7表达的改变与增殖、凋亡、迁移、侵袭、血管生成和肿瘤生长的活动相关。此外，CXCR 7的表达能够调节促血管生成因子IL-8或VEGF的表达，这可能参与了肿瘤血管生成的调节。最后，我们发现膀胱癌细胞中CXCR 7的信号传导激活了AKT、ERK和STAT 3通路。AKT和ERK信号通路可能共同调控膀胱癌的发生、发展，参与膀胱癌上皮细胞向间质细胞转化（EMT）的过程。同时使用U 0126和LY 294002抑制剂或使用CCX 733，选择性CXCR 7拮抗剂显著降低CXCR 7诱导的EMT过程。综合考虑，我们的数据首次显示CXCR 7在膀胱癌的发展中起作用。靶向CXCR 7或其下游激活的AKT和ERK通路可能有助于预防转移，并为膀胱癌提供更有效的治疗策略。(C)2012 Elsevier Inc. All rights reserved.
Bladder cancer is one of the most common tumors of the genitourinary tract; however, the molecular events underlying growth and invasion of the tumor remain unclear. Here, role of the CXCR7 receptor in bladder cancer was further explored. CXCR7 protein expression was examined using high-density tissue microarrays. Expression of CXCR7 showed strong epithelial staining that correlated with bladder cancer progression. In vitro and in vivo studies in bladder cancer cell lines suggested that alterations in CXCR7 expression were associated with the activities of proliferation, apoptosis, migration, invasion, angiogenesis and tumor growth. Moreover, CXCR7 expression was able to regulate expression of the proangiogenic factors IL-8 or VEGF, which may involve in the regulation of tumor angiogenesis. Finally, we found that signaling by the CXCR7 in bladder cancer cells activates AKT, ERK and STAT3 pathways. The AKT and ERK pathways may reciprocally regulate, which are responsible for in vitro and in vivo epithelial to mesenchymal transition (EMT) process of bladder cancer. Simultaneously targeting the two pathways by using U0126 and LY294002 inhibitors or using CCX733, a selective CXCR7 antagonist drastically reduced CXCR7-induced EMT process.Taken together, our data show for the first time that CXCR7 plays a role in the development of bladder cancer. Targeting CXCR7 or its downstream-activated AKT and ERK pathways may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for bladder cancer. (C) 2012 Elsevier Inc. All rights reserved.