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

Author

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  • Xiaolei Song

    (The Johns Hopkins University School of Medicine
    Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine)

  • Raag D. Airan

    (The Johns Hopkins University School of Medicine
    Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine)

  • Dian R. Arifin

    (The Johns Hopkins University School of Medicine
    Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine)

  • Amnon Bar-Shir

    (The Johns Hopkins University School of Medicine
    Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine)

  • Deepak K. Kadayakkara

    (The Johns Hopkins University School of Medicine
    Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine)

  • Guanshu Liu

    (The Johns Hopkins University School of Medicine
    F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute)

  • Assaf A. Gilad

    (The Johns Hopkins University School of Medicine
    Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine)

  • Peter C. M. van Zijl

    (The Johns Hopkins University School of Medicine
    F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute)

  • Michael T. McMahon

    (The Johns Hopkins University School of Medicine
    F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute)

  • Jeff W. M. Bulte

    (The Johns Hopkins University School of Medicine
    Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, the Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine
    F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute)

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.

Suggested Citation

  • 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, 2015. "Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells," Nature Communications, Nature, vol. 6(1), pages 1-7, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7719
    DOI: 10.1038/ncomms7719
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