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

Nat Commun. 2015 Mar 27:6:6719. doi: 10.1038/ncomms7719.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Glycosylation*
  • HT29 Cells
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, SCID
  • Molecular Imaging / methods
  • Mucin-1 / metabolism*
  • Neoplasm Transplantation

Substances

  • MUC1 protein, human
  • Mucin-1