Differences in CD75s- and iso-CD75s-ganglioside content and altered mRNA expression of sialyltransferases ST6GAL1 and ST3GAL6 in human hepatocellular carcinomas and nontumoral liver tissues

Abstract

The sialic acid-specific cytotoxic lectin viscumin and its recombinant equivalent rViscumin specifically bind to CD75s-gangliosides with terminal Neu5Acα6Galβ4GlcNAc sequence. We, therefore, comparatively analyzed the content of CD75s-gangliosides and closely related iso-CD75s-gangliosides (terminated by Neu5Acα3Galβ4GlcNAc sequence) and the gene expression of associated β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) and β-galactoside α-2,3-sialyltransferase 6 (ST3GAL6), respectively, in 35 hepatocellular carcinoma (HCC) patients. Ganglioside structures were identified in lipid extracts of matched pairs of malignant and nonmalignant liver tissues by thin-layer chromatography immunodetection coupled with infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry. CD75s- and iso-CD75s-gangliosides were found to be deregulated in tumor tissues and showed an elevated occurrence in 35 and 41% of HCCs, respectively, compared with nontumoral liver tissues. Statistical analysis revealed a correlation between enhanced iso-CD75s-ganglioside amount and a poor histopathological differentiation (τ = 0.317, P = 0.045) and a significant association of CD75s- and iso-CD75s-ganglioside levels in nontumorous (τ = 0.392, P = 0.003) and in tumorous tissues (τ = 0.650, P < 0.001). Quantitative real-time polymerase chain reaction gene expression analysis of sialyltransferases exhibited no difference in ST6GAL1 expression in cancerous and adjacent noncancerous tissues. Interestingly, the ST3GAL6 expression was significantly diminished in HCCs (P = 0.003). The results indicate that the occurrence of CD75s- and iso-CD75s-gangliosides in tumor tissues is largely independent of the transcriptional expression of ST6GAL1 and ST3GAL6, respectively. Thus, further experiments are required to explore the rationale behind the differential ganglioside level and to validate the applicability of CD75s- and iso-CD75s-gangliosides as targets for individual HCC therapies.

Mechanisms of cancer-associated glycosylation changes

“…In colon cancer, ST6Gal.1 over-expression leads also to the expression of an α1,2-fucosylated variant of Sia6LacNAc: the STH2 antigen (Fucα1-2(NeuAcα2-6)Galβ1-4GlcNAcβ1-3Galβ1-4Glc-Cer) (114). In human hepatocarcinomas, only a minority of the patients exhibits increased ST6Gal.1 expression (115), while ST6Gal.1 and α2,6-sialylated glycans show an altered distribution (116,117). In breast cancer, high ST6Gal.1 is associated with poor prognosis markers, such as high grade and absence of progesterone receptor (118).…”

Aberrant fucosylation of glycosphingolipids in human hepatocellular carcinoma tissues

“…Previous studies with HCC patients have focused on the abnormal expression of glycoproteins (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Souady et al recently reported that CD75s-and iso-CD75s-ganglioside expression in HCC cells is associated with poor histopathological differentiation (19). However, knowledge about neutral GSLs in HCC is lacking.…”

Sialyltransferase ST3GAL6 mediates the effect of microRNA‐26a on cell growth, migration, and invasion in hepatocellular carcinoma through the protein kinase B/mammalian target of rapamycin pathway

“…(21)(22)(23) A study has shown that ST3GAL6 expression was significantly reduced in HCC. (24) However, in our previous study, we found that ST3GAL6 was upregulated in MHCC97-H cells relative to MHCC97-L cells. (25) To further investigate the effect of ST3GAL6 in HCC, we measured the ST3GAL6 expression level in HCC cells and tissues relative to non-cancerous cells and tissues.…”