Tumour-associated carbohydrate antigens in breast cancer

Aurélie Cazet,Philippe Delannoy,Joy Burchell,Sylvain Julien,Marie Bobowski

doi:10.1186/bcr2577

Abstract

Glycosylation changes that occur in cancer often lead to the expression of tumour-associated carbohydrate antigens. In breast cancer, these antigens are usually associated with a poor prognosis and a reduced overall survival. Cellular models have shown the implication of these antigens in cell adhesion, migration, proliferation and tumour growth. The present review summarizes our current knowledge of glycosylation changes (structures, biosynthesis and occurrence) in breast cancer cell lines and primary tumours, and the consequences on disease progression and aggressiveness. The therapeutic strategies attempted to target tumour-associated carbohydrate antigens in breast cancer are also discussed.

Highlights

Glycosylation is one of the most important modifications of proteins and lipids
Sialyl-Lewisx antigens are the ligands for selectins and are involved in the recruitment of leukocytes to lymphoid tissues and inflammation sites [1]
*Correspondence: philippe.delannoy@univ-lille1.fr 1Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Sciences and Technologies of Lille, 59655 Villeneuve d’Ascq, France Full list of author information is available at the end of the article sLex, s-Lea and sialyl-Thomsen-nouvelle are tumour-associated antigens found in breast cancer [4,5,6]. When these antigens are detected at the surface of breast carcinoma cells, they are usually associated with a poor prognosis and a reduced overall survival of the patients [7]

Summary

Introduction

Glycosylation is one of the most important modifications of proteins and lipids. The structure of glycans is highly diversified and their biosynthesis requires specific enzymatic machinery involving a high number of glycosyltransferases. Several studies have shown that masking T antigens with specific peptides [92] or mAbs [93] can inhibit interaction of breast cancer cells with the endothelium and protect from metastasis One advantage of this approach is that the lectin(s) recognizing the TACA does not need to be identified to block the interaction. Abbreviations C1β3GalT, Core β1,3-galactosyltransferase (EC 2.4.1.122); GT, glycosyltransferase; HPA, Helix pomiata agglutinin; IDC, invasive ductal carcinoma; Le, Lewis; mAb, monoclonal antibody; MGL, macrophage galactose-type lectin; ORF, open reading frame; PNA, Arachis hypogea agglutinin; sLe, sialyl-Lewis; sTn, sialyl-Thomsen-nouvelle; T, ThomsenFriedenreich; TACA, tumour-associated carbohydrate antigen; Tn, Thomsennouvelle; VVA, Vicia villosa agglutinin isolectin B4. Competing interests The authors declare that they have no competing interests

Varki A

Findings

91. Taniguchi A