Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells

Xiaolei Song, Raag D. Airan, Dian R. Arifin, Amnon Bar-Shir, Deepak K. Kadayakkara, Guanshu Liu, Assaf A. Gilad, Peter C. M. van Zijl, Michael T. McMahon and Jeff W. M. Bulte ()
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Xiaolei Song: The Johns Hopkins University School of Medicine
Raag D. Airan: The Johns Hopkins University School of Medicine
Dian R. Arifin: The Johns Hopkins University School of Medicine
Amnon Bar-Shir: The Johns Hopkins University School of Medicine
Deepak K. Kadayakkara: The Johns Hopkins University School of Medicine
Guanshu Liu: The Johns Hopkins University School of Medicine
Assaf A. Gilad: The Johns Hopkins University School of Medicine
Peter C. M. van Zijl: The Johns Hopkins University School of Medicine
Michael T. McMahon: The Johns Hopkins University School of Medicine
Jeff W. M. Bulte: The Johns Hopkins University School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-7

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7719

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