Journal Article


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

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 (p<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.

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Authors

Bapu, D
Runions, J
Kadhim, M
Brooks, S

Oxford Brookes departments

Faculty of Health and Life Sciences\Department of Biological and Medical Sciences

Dates

Year of publication: 2016
Date of RADAR deposit: 2017-03-15


Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License


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This RADAR resource is the Accepted Manuscript of N-acetylgalactosamine glycans function in cancer cell adhesion to endothelial cells: a role for truncated O-glycans in metastatic mechanisms

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