Head and neck cancer N-glycome traits are cell line and HPV status-dependent

Rasheduzzaman, M; Murugan, AVM; Zhang, X; Oliveira, T; Dolcetti, R; Kenny, L; Johnson, NW; Kolarich, D; Punyadeera, C

Author(s): Rasheduzzaman, M; Murugan, AVM; Zhang, X; Oliveira, T; Dolcetti, R; Kenny, L; Johnson, NW; Kolarich, D; Punyadeera, C;
Details: Publication Year 2022-12,Volume 414,Issue #29-30,Page 8401-8411
Journal Title: Analytical and Bioanalytical Chemistry
Publication Type: Research article
Abstract: Glycosylation is the most common post-translational modification of proteins, and glycosylation changes at cell surfaces are frequently associated with malignant epithelia including head and neck squamous cell carcinoma (HNSCC). In HNSCC, 5-year survival remains poor, averaging around 50% globally: this is partly related to late diagnosis. Specific protein glycosylation signatures on malignant keratinocytes have promise as diagnostic and prognostic biomarkers and as therapeutic targets. Nevertheless, HNSCC-specific glycome is to date largely unknown. Herein, we tested six established HNSCC cell lines to capture the qualitative and semi-quantitative N-glycome using porous graphitized carbon liquid chromatography coupled to electrospray ionisation tandem mass spectrometry. Oligomannose-type N-glycans were the predominant features in all HNSCC cell lines analysed (57.5-70%). The levels of sialylated N-glycans showed considerable cell line-dependent differences ranging from 24 to 35%. Importantly, alpha2-6 linked sialylated N-glycans were dominant across most HNSCC cell lines except in SCC-9 cells where similar levels of alpha2-6 and alpha2-3 sialylated N-glycans were observed. Furthermore, we found that HPV-positive cell lines contained higher levels of phosphorylated oligomannose N-glycans, which hint towards an upregulation of lysosomal pathways. Almost all fucose-type N-glycans carried core-fucose residues with just minor levels (< 4%) of Lewis-type fucosylation identified. We also observed paucimannose-type N-glycans (2-5.5%), though in low levels. Finally, we identified oligomannose N-glycans carrying core-fucose residues and confirmed their structure by tandem mass spectrometry. This first systematic mapping of the N-glycome revealed diverse and specific glycosylation features in HNSCC, paving the way for further studies aimed at assessing their possible diagnostic relevance.
Keywords: Humans; Fucose/metabolism; Squamous Cell Carcinoma of Head and Neck; *Papillomavirus Infections; Polysaccharides/metabolism; Cell Line; *Head and Neck Neoplasms; Glycomics; Hpv; Head and neck cancers; N-glycosylation; Sialic acid
Department(s): Laboratory Research
PubMed ID: 36289103
Publisher's Version: https://doi.org/10.1007/s00216-022-04376-x
Open Access at Publisher's Site: https://doi.org/10.1007/s00216-022-04376-x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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