Aberrant Glycosylation as Biomarker for Cancer: Focus on CD43

Franca Maria Tuccillo,Antonella Borrelli,Giuseppe Fiume,Annamaria De Laurentiis,Ileana Quinto,Pierfrancesco Tassone,Franco Maria Buonaguro,Camillo Palmieri,Iris Scala,Giuseppe Scala,Patrizia Bonelli

doi:10.1155/2014/742831

Abstract

Glycosylation is a posttranslational modification of proteins playing a major role in cell signalling, immune recognition, and cell-cell interaction because of their glycan branches conferring structure variability and binding specificity to lectin ligands. Aberrant expression of glycan structures as well as occurrence of truncated structures, precursors, or novel structures of glycan may affect ligand-receptor interactions and thus interfere with regulation of cell adhesion, migration, and proliferation. Indeed, aberrant glycosylation represents a hallmark of cancer, reflecting cancer-specific changes in glycan biosynthesis pathways such as the altered expression of glycosyltransferases and glycosidases. Most studies have been carried out to identify changes in serum glycan structures. In most cancers, fucosylation and sialylation are significantly modified. Thus, aberrations in glycan structures can be used as targets to improve existing serum cancer biomarkers. The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. In this review, we discuss the aberrant protein glycosylation associated with human cancer and the identification of protein glycoforms as cancer biomarkers. In particular, we will focus on the aberrant CD43 glycosylation as cancer biomarker and the potential to exploit the UN1 monoclonal antibody (UN1 mAb) to identify aberrant CD43 glycoforms.

Highlights

Protein glycosylation is the most common and complex posttranslational modification involved in many physiological events, including protein folding and trafficking, cell-cell and cell-matrix interactions, cellular differentiations and the immune response [1,2,3,4,5]
CA19-9 assay detects aberrant sialyl Lewisa glycan (SLea) that is expressed on glycolipids and glycoprotein in patients with gastrointestinal malignancies
Alterations of the CD43 glycosylation pattern were associated with severe immunodeficiency [148, 149]. These findings indicate that an aberrant expression of CD43 glycoforms may have a role in cancer development [144, 145, 150, 151]

Summary

Introduction

Protein glycosylation is the most common and complex posttranslational modification involved in many physiological events, including protein folding and trafficking, cell-cell and cell-matrix interactions, cellular differentiations and the immune response [1,2,3,4,5]. Glycosylation is not a templatebased process such as DNA, RNA, or protein synthesis but is rather based on the balance achieved by the expression and activity levels of the different enzymes involved in the glycosylation process, such as glycosyltransferases and glycosidases, and on the availability of precursor monosaccharide molecules, which in turn depends on the availability of nutrient resources and expression of enzymes responsible for their synthesis and interconversion [3, 4, 7, 8] This highly increases the complexity of the protein glycosylation process and the molecular microheterogeneity of glycoproteins [9]. Despite the wide diversity of glycan structures, only a few distinct glycan changes are associated with malignant transformation and tumour progression This suggests that specific glycosylation patterns correlate with tumour progression, likely due to gain of function in cell fitness and survival [12]. The interactions of lectins with tumour cell glycans can promote tumour progression

Altered Glycosylation Patterns in Cancer

Glycan-Based Serological Assays in Cancer

CD43 Is a Mucin-Type Cancer-Associated Glycoprotein

UN1 Monoclonal Antibody Recognizes Cancer-Associated CD43 Glycoforms

Conclusions