Understanding and exploiting changes in O-linked glycosylation in breast cancer
© BioMed Central Ltd 2008
Published: 13 May 2008
The differences in glycosylation patterns seen in breast malignancy strongly influence the final structure of membrane and secreted glycoproteins, and these novel tumour-associated glycoforms can modify the behaviour of the malignant cell and its interaction with immune effector cells. Changes in mucin type O-glycosylation occur in breast carcinomas and are the result, at least in part, of changes in the expression of specific glycosyltransferases . A similar change in the expression of glycosyltransferases resulting in the change of glycans attached to O-linked glycoproteins is seen when normal dendritic cells mature and migrate to the lymph nodes . As 70% to 80% of metastatic breast cancers metastasize via the lymphatics, a particular pattern of O-linked glycans may be required for cells to migrate and/or settle in the lymph nodes.
Changes in O-linked glycosylation have a considerable influence on the structure of mucin glycoproteins that carry hundreds of O-linked glycans. The MUC1 membrane mucin is expressed by over 90% of breast carcinomas and in the change to malignancy truncated O-glycans are added to this mucin. In vitro synthesis of MUC1-based glycoproteins and glycopeptides carrying specific tumour-associated glycans has allowed an investigation of how individual glycoforms affect the immune response and interact with immune effector cells [3, 4]. It is becoming clear that some glycoforms of MUC1 can induce an immune response while others are immunosuppressive. Understanding how the different tumour-associated glycoforms induce or inhibit the immune response is important for the design of clinical studies using MUC1-based antigens.
Supported by Cancer Research UK, European Commission and Breast Cancer Campaign. The authors would like to thanks all members of the European Prime Boost Consortium, contract number QLK3-CT-2002-02010.
- Burchell JM, Mungul A, Taylor-Papapdimitriou J: O-linked glycosylation in the mammary gland: changes that occur during malignancy. J Mammary Gland Biol Neoplasia. 2001, 6: 355-364. 10.1023/A:1011331809881.View ArticlePubMedGoogle Scholar
- Julien S, Grimshaw M, Sutton-Smith M, Coleman J, Dell A, Taylor-Papadimitriou J, Burchell J: O-linked glycosylation is regulated during maturation of dendritic cells and has an impact on their migration. J Immunol. 2007, 179: 5701-5710.View ArticlePubMedGoogle Scholar
- Napoletano C, Rughetti A, Tarp MPA, Coleman J, Bennett EP, Picco G, Sale P, Denda-Nagai K, Irimura T, Mandel U, Clausen H, Frati L, Taylor-Papadimitriou J, Burchell J, Nuti M: Tumor associated Tn-MUC1 glycoform is internalised through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells. Cancer Res. 2007, 67: 8358-8367. 10.1158/0008-5472.CAN-07-1035.View ArticlePubMedGoogle Scholar
- Tarp MA, Sorensen AL, Mandel U, Paulsen H, Burchell J, Taylor-Papadimitriou J, Clausen H: Identification of a novel cancer-specific immunodominant glycopeptide epitope in the MUC1 tandem repeat. Glycobiology. 2007, 17: 197-209. 10.1093/glycob/cwl061.View ArticlePubMedGoogle Scholar