title: 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.
authors.affiliation: Institute of Medical Physics and Biophysics, University of Münster, Germany.
authors.forename: Jamal
authors.initials: J
authors.lastname: Souady
authors.forename: Marcel
authors.initials: M
authors.lastname: Hülsewig
authors.forename: Ute
authors.initials: U
authors.lastname: Distler
authors.forename: Jörg
authors.initials: J
authors.lastname: Haier
authors.forename: Axel
authors.initials: A
authors.lastname: Denz
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.forename: Norbert
authors.initials: N
authors.lastname: Senninger
authors.forename: Klaus
authors.initials: K
authors.lastname: Dreisewerd
authors.forename: Jasna
authors.initials: J
authors.lastname: Peter-Katalinic
authors.forename: Johannes
authors.initials: J
authors.lastname: Müthing
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D015331:Cohort Studies; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015394:Molecular Structure; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D047368:Tumor Burden; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D005732:Gangliosides; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; C000722087:ST3GAL1 protein, human