Volume 10 Supplement 2

Breast Cancer Research 2008

Open Access

Understanding and exploiting changes in O-linked glycosylation in breast cancer

  • S Julien1,
  • J Coleman1,
  • G Picco1,
  • R Beatson1,
  • J Taylor-Papadimitriou1 and
  • J Burchell1
Breast Cancer Research200810(Suppl 2):P29

https://doi.org/10.1186/bcr1913

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 [1]. 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 [2]. 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.

Declarations

Acknowledgements

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.

Authors’ Affiliations

(1)
Breast Cancer Biology, King's College London School of Medicine, Guy's Hospital

References

  1. 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
  2. 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
  3. 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
  4. 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

Copyright

© BioMed Central Ltd 2008

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