Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-AssociatedN-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 B-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 GlcNAcexpressing 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. [Cancer Res 2009;69(14):5811-9]

Role of the Unfolded Protein Response in Regulating the Mucin-Dependent Filamentous-Growth Mitogen-Activated Protein Kinase Pathway

“…Given that highly specific changes in glycosylation regulate diverse proteins like Notch (130), dystroglycan (131)(132)(133), amyloid precursor protein (134,135), and MUC1 (136), one can speculate that UPR regulates these proteins under some conditions. For example, in cancer cells, the global glycosylation of proteins is impacted (137,138), which includes MUC1, a major activator of the proliferative RAS-MEK-ERK MAPK pathway (9,139,140). Aberrantly glycosylated MUC1 and other proteins may be recognized by QC pathways in this setting, which may impact signaling pathway outputs.…”

A Nanoparticle-Lectin Immunoassay Improves Discrimination of Serum CA125 from Malignant and Benign Sources

“…TRF for europium was measured (ex: 340 nm; em: 615 nm) using Victor ™ 1420 Multilabel counter (Perkin-Elmer Life Sciences), and after adding enhancement solution and incubating for 10 min with shaking the TRF signal was measured. For the TRF CA125 lectin-NPs assay, 100 L assay buffer (with an additional 6 mmol/L CaCl 2 ) containing 1ϫ10 7 Eu-NPs coated with lectin was added to each well for 2 h at room temperature with shaking. After incubation, the wells were washed 6 times with wash buffer.…”

N-Glycosylation of Asparagine 8 Regulates Surface Expression of Major Histocompatibility Complex Class I Chain-related Protein A (MICA) Alleles Dependent on Threonine 24

“…established that a change in the cellular N-glycan profile is associated with malignant transformation and increased metastasis (50,51). A specific increase in the amount of highly complex N-glycans has been observed in melanomas, as well as breast and colon cancers (52).…”