Clinical relevance and functional role of galectin-1 in hepatocellular carcinoma

Abstract

INTRODUCTION: Hepatocellular carcinoma (HCC) has one the world’s leading cancer incidences and despite extensive research, the numbers of HCC-causing deaths remain high, accounting for the 3rd leading cause of cancer death. Galectins are b-galactose specific binding proteins, which in turn facilitate the crosslinking of molecules and thus enabling vital cell-cell and cell-matrix interactions and signal transduction. Galectin-1 (Gal1), the first identified member of the galectin family, has been found to regulate cell processes; both intracellularly and extracellularly upon its secretion. The oncogenic role of gal1 in HCC has been increasingly studied, however, ambiguities concerning its non-classical secretion mechanism and any associated signalling pathways remain undisclosed. This study aims to further understand the clinical relevance and functional role of Gal1 in HCC tumourigenesis. MATERIALS AND METHODS: Clinical analysis of Gal1 was conducted with human HCC cell lines and patient RNA samples by quantitative real time PCR. ELISA analysis further highlighted the clinical relevance of Gal1 in detecting the secretory gal1 levels in patient blood serum samples. The functional role of Gal1 in HCC was subsequently explored in migration, invasion and soft agar assays after the stable expression of Gal1 in HCC cell lines. RESULTS AND DISCUSSION: Analysis of 48 HCC clinical samples revealed the significantly higher Gal1 expression in HCC late stage tumours compared to early stage. This overexpression was also observed in immunohistological staining of tumour tissues and elevated gal1 levels in patient blood serum samples. Overexpression corresponded to poorer disease-free survival, cirrhotic liver and venous invasion. By knocking down Gal1 expression in HCC cell lines BEL7402 and MHCC97L, functional experiment results showed reduced migration, invasion and anchorage independent growth. Similarly, when Gal1 was overexpressed in HCC cell line PLC/PRF/5, the migratory potential and the ability for anchorage independent growth increased. These results signify the importance of gal1 in regulating essential tumourigenic cell processes. CONCLUSION: Gal1 expression is significantly higher in HCC patient samples observed in the clinical setting and likewise in HCC cell lines. The oncogenic role of Gal1 has been implicated in HCC tumourigenesis by promoting cell migration, invasion and anchorage independent growth.