Abstract
Alterations in mucin expression and glycosylation are associated with cancer development. Underglycosylated mucin-1 (uMUC1) is overexpressed in most malignant adenocarcinomas of epithelial origin (for example, colon, breast and ovarian cancer). Its counterpart MUC1 is a large polymer rich in glycans containing multiple exchangeable OH protons, which is readily detectable by chemical exchange saturation transfer (CEST) MRI. We show here that deglycosylation of MUC1 results in >75% reduction in CEST signal. Three uMUC1+ human malignant cancer cell lines overexpressing uMUC1 (BT20, HT29 and LS174T) show a significantly lower CEST signal compared with the benign human epithelial cell line MCF10A and the uMUC1− tumour cell line U87. Furthermore, we demonstrate that in vivo CEST MRI is able to make a distinction between LS174T and U87 tumour cells implanted in the mouse brain. These results suggest that the mucCEST MRI signal can be used as a label-free surrogate marker to non-invasively assess mucin glycosylation and tumour malignancy.
Highlights
Alterations in mucin expression and glycosylation are associated with cancer development
We show here that underglycosylated MUC1 (uMUC1) þ human malignant cancer cell lines exhibit a significantly lower chemical exchange saturation transfer (CEST) signal compared with a benign human epithelial cell line and an uMUC1 À tumour cell line
We have demonstrated that mucCEST magnetic resonance imaging (MRI) is able to differentiate between tumour cells that are expressing normal versus underglycosylated MUC1
Summary
Alterations in mucin expression and glycosylation are associated with cancer development. We demonstrate that in vivo CEST MRI is able to make a distinction between LS174T and U87 tumour cells implanted in the mouse brain These results suggest that the mucCEST MRI signal can be used as a label-free surrogate marker to non-invasively assess mucin glycosylation and tumour malignancy. Targeted imaging agents against the uMUC1 antigen recognizing the exposed peptide sequence on the tandem repeat have been developed, including radiolabelled agents[15,17,20] and a dual-modality probe with the near-infrared fluorescence (NIRF) dye Cy5.5 conjugated to MRI-detectable superparamagnetic iron oxide nanoparticles[21,22]. MucCEST imaging represents a novel label-free imaging technique to non-invasively probe mucin glycosylation and tumour malignancy
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