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Cancer Lett. 2016 Jun 1;375(2):367-374. doi: 10.1016/j.canlet.2016.03.019. Epub 2016 Mar 16.

N-acetylgalactosamine glycans function in cancer cell adhesion to endothelial cells: A role for truncated O-glycans in metastatic mechanisms.

Author information

1
Department of Biological & Medical Sciences, Faculty of Health & Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3ā€‰0BP, UK.
2
Department of Biological & Medical Sciences, Faculty of Health & Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3ā€‰0BP, UK. Electronic address: sbrooks@brookes.ac.uk.

Abstract

Failure in O-glycan chain extension exposing Tn antigen (GalNAc-O-Ser/Thr) is clinically associated with cancer metastasis. This study provides evidence of a functional role for aberrant GalNAc-glycans in cancer cell capture from blood flow and/or adhesion to endothelium. Adhesion of breast cancer cells to human umbilical vein endothelial cell monolayers was modelled under sweeping flow. Adhesion of metastatic, GalNAc glycan-rich, MCF7 and ZR 75 1 cells to endothelium increased over timepoints up to 1.5 hour, after which it plateaued. Adhesion was significantly inhibited (pā€‰<ā€‰0.001) when cell surface GalNAc-glycans were masked, an effect not seen in GalNAc glycan-poor, non-metastatic BT 474 cells. Masking irrelevant galactose- and mannose-glycans had no inhibitory effect. Imaging of cells post-adhesion over a 24 hour time course using confocal and scanning electron microscopy revealed that up to 6 hours post-adhesion, motile, rounded cancer cells featuring lamellipodia-like processes crawled on an intact endothelial monolayer. From 6-12 hours post-adhesion, cancer cells became stationary, adopted a smooth, circular flattened morphology, and endothelial cells retracted from around them leaving cleared zones in which the cancer cells proceeded to form colonies through cell division.

KEYWORDS:

Helix pomatia agglutinin; Tn antigen; adhesion; glycosylation; metastasis

PMID:
26994652
DOI:
10.1016/j.canlet.2016.03.019
[Indexed for MEDLINE]

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