Glycoengineered cell models for the characterization of cancer O-glycoproteome: an innovative strategy for biomarker discovery

Abstract

Glycosylation is one of the most abundant forms of protein posttranslational modification. O-glycosylation is a major type of protein glycosylation, comprising different types and structures expressed in several physiologic and pathologic conditions. The understanding of protein attachment site and glycan structure is of the utmost importance for the clarification of the role glycosylation plays in normal cells and in pathological conditions. Neoplastic transformation frequently shows the expression of immature truncated O-glycans. These aberrantly expressed O-glycans have been shown to induce oncogenic properties and can be detected in premalignant lesions, meaning that they are an important source of biomarkers. This article addresses the recent application of genetically engineered cancer cell models to produce simplified homogenous O-glycans allowing the characterization of cancer cells O-glycoproteomes, using advanced mass spectrometry methods and the identification of potential cancer-specific O-glycosylation sites. This article will also discuss possible applications of these biomarkers in the cancer field.

Keywords:

• cancer biomarkers
• glycobiomarkers
• glycosylation

Financial & competing interests disclosure

IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. The authors were supported by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the FCT-Foundation for Science and Technology, under the projects: PEst-C/SAU/LA0003/2013 and PTDC/BBB-EBI/0786/2012. D Campos has received a grant from the FCT (grant number: SFRH/BD/73717/2010). D Freitas has received a grant from the FCT (grant number: PD/BI/105913/2014).

Key issues

• Mucin-type O-glycosylation is a common and diverse form of posttranslational protein modification. These different structures are expressed with cell and tissue specificity and show major alterations in pathologic conditions. These major changes include the expression of immature truncated O-glycans, such as Tn and STn antigens.

• The development of genetically engineered cell models, combined with liquid chromatography tandem mass spectrometry with electron transfer dissociation for glycan site specification, has allowed the characterization of the O-glycoproteome of cancer cells.

• The O-glycoproteome of cancer cells constitutes a major source of O-glycoproteins identification and opens for their potential as biomarkers of this disease and can provide massive information contained in the glyco-code of a cancer cell.