Glycosylation characteristics of colorectal cancer.

Glycans on proteins and lipids are known to alter with malignant transformation. The study of these may contribute to the discovery of biomarkers and treatment targets as well as understanding of cancer biology. We here describe the change of glycosylation specifically defining colorectal cancer with view on N-glycans, O-glycans, and glycosphingolipid glycans in colorectal cancer cells and tissues as well as patient sera. Glycan alterations observed in colon cancer include increased β1,6-branching and correlating higher abundance of (poly-)N-acetyllactosamine extensions of N-glycans as well as an increase in (truncated) high-mannose type glycans, while bisected structures decrease. Colorectal cancer-associated O-glycan changes are predominated by reduced expression of core 3 and 4 glycans, whereas higher levels of core 1 glycans, (sialyl) T-antigen, (sialyl) Tn-antigen, and a generally higher density of O-glycans are observed. Specific changes for glycosphingolipid glycans are lower abundances of disialylated structures as well as globo-type glycosphingolipid glycans with exception of Gb3. In general, alterations affecting all discussed glycan types are increased sialylation, fucosylation as well as (sialyl) Lewis-type antigens and type-2 chain glycans. As a consequence, interactions with glycan-binding proteins can be affected and the biological function and cellular consequences of the altered glycosylation with regard to tumorigenesis, metastasis, modulation of immunity, and resistance to antitumor therapy will be discussed. Finally, analytical approaches aiding in the field of glycomics will be reviewed with focus on binding assays and mass spectrometry.