CCL18 enhances migration, invasion and EMT by binding CCR8 in bladder cancer cells

Liu,Xiaoqiang; Xu,Xiangyun; Deng,Wen; Huang,Mingchuan; Wu,Yanlong; Zhou,Zhengtao; Zhu,Ke; Wang,Yibing; Cheng,Xinfu; Zhou,Xiaochen; Chen,Luyao; Li,Yu; Wang,Gongxian; Fu,Bin

doi:10.3892/mmr.2018.9791

CCL18 enhances migration, invasion and EMT by binding CCR8 in bladder cancer cells

Authors:
- Xiaoqiang Liu
- Xiangyun Xu
- Wen Deng
- Mingchuan Huang
- Yanlong Wu
- Zhengtao Zhou
- Ke Zhu
- Yibing Wang
- Xinfu Cheng
- Xiaochen Zhou
- Luyao Chen
- Yu Li
- Gongxian Wang
- Bin Fu
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Affiliations: Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Urology, The Third Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Emergency, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Urology, The Second People's Hospital of Jingdezhen, Jingdezhen, Jiangxi 333000, P.R. China
Published online on: December 24, 2018 https://doi.org/10.3892/mmr.2018.9791
Pages: 1678-1686
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increased expression of CCL18 has been observed in various malignancies and in the urine samples of patients with bladder cancer (BC). However, the roles of CCL18 in the development, progression and metastasis of BC remain unclear. The present study demonstrated that CCL18 expression was significantly associated with advanced clinical stages of BC. Furthermore, exogenous CCL18 promoted cell invasion and migration, and induced cell epithelial‑mesenchymal transition (EMT) in BC cells. Western blotting demonstrated that E‑cadherin, an epithelial marker, was decreased, whereas matrix metalloproteinase (MMP)‑2 and vascular endothelial growth factor (VEGF)‑C were increased in CCL18‑treated cells. Blocking CCR8 via a small molecule inhibitor or short hairpin (sh)RNA mitigated the decrease in E‑cadherin, and increase in MMP‑2 and VEGF‑C, caused by human recombinant (r)CCL18. CCR8 knockdown by shRNA reversed rCCL18‑induced cancer cell invasion, migration and EMT. In conclusion, these data suggested that CCL18 may promote migration, invasion and EMT by binding CCR8 in BC cells. Inhibition of CCL18 activity by blocking CCR8 could be a potential therapeutic strategy for preventing the progression of BC.

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