title: Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to Malignancy.
abstract: Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O-glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, α2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response.
authors.affiliation: Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furukawa
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Piao
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Shinohara
mesh_terms: D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006017:Glycolipids / Q000378:metabolism; D054794:Glycomics / Q000379:methods; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D060787:Neoplasm Grading; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D006017:Glycolipids; D006023:Glycoproteins; D011134:Polysaccharides