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Understanding and exploiting changes in O-linked glycosylation in breast cancer
Breast Cancer Research volume 10, Article number: P29 (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.
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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.
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Julien, S., Coleman, J., Picco, G. et al. Understanding and exploiting changes in O-linked glycosylation in breast cancer. Breast Cancer Res 10, P29 (2008) doi:10.1186/bcr1913
- Breast Cancer
- Breast Carcinoma
- Metastatic Breast Cancer
- Metastatic Breast