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

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.