Altered aquaporin 9 expression and localization in human hepatocellular carcinoma

Background

In addition to the biochemical components secreted in bile, aquaporin (AQP) water channels exist in hepatocyte membranes to form conduits for water movement between the sinusoid and the bile canaliculus. The aim of the current study was to analyse AQP 9 expression and localization in human hepatocellular carcinoma (HCC) and non-tumourigenic liver (NTL) tissue from patients undergoing hepatic resection.

Methods

Archived tissue from 17 patients was sectioned and analysis performed using an antibody raised against AQP 9. Slides were blind-scored to determine AQP 9 distribution within HCC and NTL tissue.

Results

Aquaporin 9 was predominantly expressed in the membranes of hepatocytes and demonstrated zonal distribution relative to hepatic sinusoid structure in normal liver. In HCC arising in the absence of cirrhosis AQP 9 remained membrane-localized with zonal distribution in the majority of NTL. By contrast, AQP 9 expression was significantly decreased in the HCC mass vs. pair-matched NTL. In HCC in the presence of cirrhosis, NTL was characterized by extensive AQP 9 staining in the membrane in the absence of zonal distribution and AQP 9 staining in NTL was significantly greater than that observed in the tumour mass.

Conclusions

These data demonstrate that human HCC is characterized by altered AQP 9 expression and AQP 9 localization in the NTL mass is dependent on underlying liver pathology. Given the central role of AQPs in normal liver function and the potential role of AQPs during transformation and progression, these data may prove valuable in future diagnostic and/or therapeutic strategies.