CC Chemokine Ligand 18 Promotes Cell Proliferation and Metastasis of Urothelial Carcinoma via Activating PI3K/mTOR Signaling in Patient with Renal Transplantation

Abstract

Objective: The study aimed to investigate the role of chemokine (C-C motif) ligand 18 (CCL18) in the progression of urothelial carcinoma (UC) after renal transplants (RT). Methods: Tissues were collected from 60 patients with UC in which 24 were after RT. The tissues were all obtained from patients after radical cystectomy. Expression levels of CCL18 were examined by immunohistochemistry, RT-polymerase chain ­reaction (RT-PCR), and quantitative RT-PCR, respectively. WST-1 assay was performed to determine proliferative capacity of UC cells. Migration and invasion of UC cells were analyzed by the using of chemotaxis and Transwell system. Western blotting was applied to assess the activation of PI3K-mTOR (Mammalian Target of Rapamycin) signaling. Results: Compared to normal urothelial tissues, the expression levels of CCL18 were significantly increased in tumors of UC, and even more in tumors of UC after RT. Ectopic expression of CCL18 efficiently enhanced the proliferation of UC cells and moreover, exacerbated the migration and invasion of UC cells. Furthermore, overexpressed CCL18 increased the phosphorylation of PI3K, Akt, and mTOR in UC cells, suggesting the hyperactivation of PI3K/Akt/mTOR signaling. Conclusions: The results demonstrate the critical role of CCL18 in the progression of UC, especially in receipt with RT. Our study indicates that CCL18 could serve as a biomarker and therapeutic target in diagnosis of recipients with UC after RT.