title: Analysis of the human cancer glycome identifies a novel group of tumor-associated N-acetylglucosamine glycan antigens.
abstract: The cell surface is covered by a dense layer of protein- and lipid-linked glycans. Although it has been known that distinct glycan structures are associated with cancer, the whole spectrum of cancer-associated glycans has remained undiscovered. In the present study, we analyzed the protein-linked cancer glycome by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric glycan profiling of cancer patient tissue samples. In lung cancer, we detected accumulation of a novel group of tumor-associated glycans. These protein-linked glycans carried abnormal nonreducing terminal beta-N-acetyl-D-glucosamine (GlcNAc) residues. A similar phenomenon was also detected in structural analyses of tumor-derived glycosphingolipids. This showed that glycan biosynthesis may dramatically change in cancer and that direct glycome analysis can detect the resulting marker glycans. Based on the structural knowledge, we further devised a covalent labeling technique for the detection of GlcNAc-expressing tumors with a specific transferase enzyme. In normal tissues, terminal GlcNAc antigens are capped by galactosylation. Similarly to common cancer-associated glycan antigens T, Tn, and sialyl-Tn, the newly discovered GlcNAc antigens result from incomplete glycosylation. In conclusion, the identified terminal GlcNAc glycans should be recognized as a novel class of tumor markers.
authors: Glykos Finland Ltd., Helsinki, Finland. tero.satomaa@glykos.fi
authors: Tero
authors: T
authors: Satomaa
authors: Annamari
authors: A
authors: Heiskanen
authors: Iréne
authors: I
authors: Leonardsson
authors: Jonas
authors: J
authors: Angström
authors: Anne
authors: A
authors: Olonen
authors: Maria
authors: M
authors: Blomqvist
authors: Noora
authors: N
authors: Salovuori
authors: Caj
authors: C
authors: Haglund
authors: Susann
authors: S
authors: Teneberg
authors: Jari
authors: J
authors: Natunen
authors: Olli
authors: O
authors: Carpén
authors: Juhani
authors: J
authors: Saarinen
mesh_terms: D000117:Acetylglucosamine / Q000032:analysis / Q000378:metabolism*; D005700:Galactosyltransferases / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000032:analysis / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D006023:Glycoproteins; D011134:Polysaccharides; D005700:Galactosyltransferases; D000117:Acetylglucosamine