Clinicopathological and Prognostic Significance of CCR5/CCL5 axis in Hepatocellular Carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the world’s most devastating malignancy which accounts for more than 90% liver cancer. The poor diagnosis of HCC lead’s scientists to search for novel treatment options to improve patient survival rates. There is accumulating evidence that chemokines and chemokine receptors (CCRs) contribute to tumor development and progression, as well as metastasis. Chemokine CCL5 (RANTES) has been reported to facilitate tumor progression and metastasis in various cancers, including liver cancer. However, the function of CCR5/CCL5 interaction in HCC proliferation and migration is poorly understood. Hence, the present study was undertaken to investigate the expression and role of the CCR5/CCL5 axis interface in the progression and invasiveness of HCC. In vitro study of liver cancer cell lines SNU387, PLC/PRF 5, and SK-HEP-1 showed higher expression of CCR5. Flow cytometry, RT-PCR, western blot, immunofluorescence techniques were used to quantify the expression of chemokine CCR5 and CCL5 in liver cancer cells. To determine the clinical significance of CCR5 expressed by HCC cell lines, a microarray of liver cancer tissues stained for CCR5 and CCL5 were analyzed. Our results show significantly (p< 0.001) higher expression of CCR5 and CCL5 in cancerous tissues compared to normal liver tissues. Furthermore, in order to delineate the role of CCR5/CCL5 interaction in HCC cell proliferation and migration, we pre-treated the HCC cell lines with the Maraviroc (CCR5 antagonist) in presence of CCL5. This data demonstrates both biological and clinical significance of CCR5 and CCL5 expression that may contribute to HCC metastasis, thus inhibition of its axis could be a promising avenue to treat liver cancer.