Probing Aberrantly Glycosylated Mucin 1 in Breast Cancer Extracellular Vesicles.

Saroj Saroj, Debashish Paul, Akbar Ali, Chrysafis Andreou, Suchetan Pal, Tatini Rakshit

ACS applied bio materials 2023 Nov 20

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Aberrantly glycosylated mucin 1 is a critical prognostic biomarker in breast epithelial cancers. Hypoglycosylated mucin 1 coats the surface of the cancer cells, where O-glycans are predominantly linked via an N-acetylgalactosamine moiety (GalNAc). Cancer cell-derived extracellular vesicles (EVs) carry biomarkers from parent cancer cells to the recipient cells and, therefore, could potentially be leveraged for diagnostics and noninvasive disease monitoring. We devised a label-free approach for identifying glycoprotein mucin 1 overexpression on breast cancer EVs. While exploring a plethora of biochemical (enzyme-linked immunosorbent assay, flow cytometry, and SDS-PAGE) and label-free biophysical techniques (circular dichroism and infrared spectroscopy (IR)) along with multivariate analysis, we discovered that mucin 1 is significantly overexpressed in breast cancer EVs and aberrant glycosylation in mucin 1 could be critically addressed using IR and multivariate analysis targeting the GalNAc sugar. This approach emerges as a convenient and comprehensive method of distinguishing cancer EVs from normal samples and holds potential for nonintrusive breast cancer liquid biopsy screening.

Citation

Saroj Saroj, Debashish Paul, Akbar Ali, Chrysafis Andreou, Suchetan Pal, Tatini Rakshit. Probing Aberrantly Glycosylated Mucin 1 in Breast Cancer Extracellular Vesicles. ACS applied bio materials. 2023 Nov 20;6(11):4944-4951