title: 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.
authors.affiliation: Department of Biological & Medical Sciences, Faculty of Health & Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3 0BP, UK.
authors.forename: Deepashree
authors.initials: D
authors.lastname: Bapu
authors.affiliation: Department of Biological & Medical Sciences, Faculty of Health & Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3 0BP, UK.
authors.forename: John
authors.initials: J
authors.lastname: Runions
authors.affiliation: Department of Biological & Medical Sciences, Faculty of Health & Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3 0BP, UK.
authors.forename: Munira
authors.initials: M
authors.lastname: Kadhim
authors.affiliation: Department of Biological & Medical Sciences, Faculty of Health & Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3 0BP, UK. Electronic address: sbrooks@brookes.ac.uk.
authors.forename: Susan Ann
authors.initials: SA
authors.lastname: Brooks
mesh_terms: D000116:Acetylgalactosamine / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D037102:Lectins / Q000378:metabolism; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D037102:Lectins; D011134:Polysaccharides; C040286:Tn antigen; D000116:Acetylgalactosamine
keywords: Helix pomatia agglutinin; Tn antigen; adhesion; glycosylation; metastasis