Analysis of the human cancer glycome identifies a novel group of tumor-associated N-acetylglucosamine glycan antigens.
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.
Satomaa
Tero
T
Glykos Finland Ltd., Helsinki, Finland. tero.satomaa@glykos.fi
Heiskanen
Annamari
A
Leonardsson
Iréne
I
Angström
Jonas
J
Olonen
Anne
A
Blomqvist
Maria
M
Salovuori
Noora
N
Haglund
Caj
C
Teneberg
Susann
S
Natunen
Jari
J
Carpén
Olli
O
Saarinen
Juhani
J
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
D006023:Glycoproteins; D011134:Polysaccharides; D005700:Galactosyltransferases; D000117:Acetylglucosamine