Adenosine A2b receptor is highly expressed in human hepatocellular carcinoma

High levels of adenosine accumulate in hypoxic tissues during the rapid growth of tumors, suggesting activation of adenosine receptors may facilitate tumor progress. The relevance of adenosine receptors to hepatocellular carcinoma (HCC), in particular the adenosine A2b receptor (A2b), is not yet fully understood. The aim of this study was to assess whether A2b was differentially expressed in normal and cancerous tissues and evaluate the clinicopathological correlation of A2b level in HCC. Expression of A2b in tumor cells was investigated by immunohistochemical staining. Protein analysis was done by Western blotting and evaluation of A2b mRNA expression levels utilized quantitative real-time PCR analysis of tissue samples of 64 hepatocellular carcinomas and in their paired adjacent normal tissues. Western blot data suggested that A2b was expressed predominantly in the cell membrane and cytoplasm of tumor cells and that the intensity of A2b protein expression was consistently higher in HCC than in adjacent normal tissues. Levels of A2b mRNA in HCC were significantly higher than in adjacent tissues, as measured by real-time PCR (P < 0.001). With regard to venous invasion, satellite lesions and advanced pathologic Tumor-Node-Metastasis (pTNM) stage, the A2b level tended to be higher than that seen in negative cases (P < 0.05). Our findings demonstrate that A2b expression is up-regulated in HCC, the expression level of A2b is correlated to tumor progression in HCC, and suggest that A2b may be a novel target for HCC therapeutic strategy.