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, Jeff W.M. Bulte

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number6719
JournalNature communications
Volume6
DOIs
StatePublished - Mar 30 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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