Loss of the endothelial glycocalyx is associated with increased E-selectin mediated adhesion of lung tumour cells to the brain microvascular endothelium

2.50
Hdl Handle:
http://hdl.handle.net/11287/593976
Title:
Loss of the endothelial glycocalyx is associated with increased E-selectin mediated adhesion of lung tumour cells to the brain microvascular endothelium
Authors:
Rai, S.; Nejadhamzeeigilani, Z.; Gutowski, Nicholas J.; Whatmore, Jacqueline L.
Abstract:
BACKGROUND: Arrest of metastasising lung cancer cells to the brain microvasculature maybe mediated by interactions between ligands on circulating tumour cells and endothelial E-selectin adhesion molecules; a process likely to be regulated by the endothelial glycocalyx. Using human cerebral microvascular endothelial cells and non-small cell lung cancer (NSCLC) cell lines, we describe how factors secreted by NSCLC cells i.e. cystatin C, cathepsin L, insulin-like growth factor-binding protein 7 (IGFBP7), vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-alpha), damage the glycocalyx and enhance initial contacts between lung tumour and cerebral endothelial cells. METHODS: Endothelial cells were treated with tumour secreted-proteins or lung tumour conditioned medium (CM). Surface levels of E-selectin were quantified by ELISA. Adhesion of A549 and SK-MES-1 cells was examined under flow conditions (1 dyne/cm(2)). Alterations in the endothelial glycocalyx were quantified by binding of fluorescein isothiocyanate-linked wheat germ agglutinin (WGA-FITC). RESULTS: A549 and SK-MES-1 CM and secreted-proteins significantly enhanced endothelial surface E-selectin levels after 30 min and 4 h and tumour cell adhesion after 30 min, 4 and 24 h. Both coincided with significant glycocalyx degradation; A549 and SK-MES-1 CM removing 55 +/- 12 % and 58 +/- 18.7 % of WGA-FITC binding, respectively. Inhibition of E-selectin binding by monoclonal anti-E-selectin antibody completely attenuated tumour cell adhesion. CONCLUSION: These data suggest that metastasising lung cancer cells facilitate their own adhesion to the brain endothelium by secreting factors that damage the endothelial glycocalyx, resulting in exposure of the previously shielded adhesion molecules and engagement of the E-selectin-mediated adhesion axis.
Citation:
J Exp Clin Cancer Res. 2015 Sep 25;34(1):105.
Publisher:
BioMed Central
Journal:
Journal of experimental & clinical cancer research : CR
Issue Date:
25-Sep-2015
URI:
http://hdl.handle.net/11287/593976
DOI:
10.1186/s13046-015-0223-9
PubMed ID:
26407999
Additional Links:
http://jeccr.biomedcentral.com/articles/10.1186/s13046-015-0223-9
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1756-9966
Appears in Collections:
2015 RD&E publications; Neurology; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRai, S.en
dc.contributor.authorNejadhamzeeigilani, Z.en
dc.contributor.authorGutowski, Nicholas J.en
dc.contributor.authorWhatmore, Jacqueline L.en
dc.date.accessioned2016-01-19T12:38:10Zen
dc.date.available2016-01-19T12:38:10Zen
dc.date.issued2015-09-25en
dc.identifier.citationJ Exp Clin Cancer Res. 2015 Sep 25;34(1):105.en
dc.identifier.issn1756-9966en
dc.identifier.pmid26407999en
dc.identifier.doi10.1186/s13046-015-0223-9en
dc.identifier.urihttp://hdl.handle.net/11287/593976en
dc.description.abstractBACKGROUND: Arrest of metastasising lung cancer cells to the brain microvasculature maybe mediated by interactions between ligands on circulating tumour cells and endothelial E-selectin adhesion molecules; a process likely to be regulated by the endothelial glycocalyx. Using human cerebral microvascular endothelial cells and non-small cell lung cancer (NSCLC) cell lines, we describe how factors secreted by NSCLC cells i.e. cystatin C, cathepsin L, insulin-like growth factor-binding protein 7 (IGFBP7), vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-alpha), damage the glycocalyx and enhance initial contacts between lung tumour and cerebral endothelial cells. METHODS: Endothelial cells were treated with tumour secreted-proteins or lung tumour conditioned medium (CM). Surface levels of E-selectin were quantified by ELISA. Adhesion of A549 and SK-MES-1 cells was examined under flow conditions (1 dyne/cm(2)). Alterations in the endothelial glycocalyx were quantified by binding of fluorescein isothiocyanate-linked wheat germ agglutinin (WGA-FITC). RESULTS: A549 and SK-MES-1 CM and secreted-proteins significantly enhanced endothelial surface E-selectin levels after 30 min and 4 h and tumour cell adhesion after 30 min, 4 and 24 h. Both coincided with significant glycocalyx degradation; A549 and SK-MES-1 CM removing 55 +/- 12 % and 58 +/- 18.7 % of WGA-FITC binding, respectively. Inhibition of E-selectin binding by monoclonal anti-E-selectin antibody completely attenuated tumour cell adhesion. CONCLUSION: These data suggest that metastasising lung cancer cells facilitate their own adhesion to the brain endothelium by secreting factors that damage the endothelial glycocalyx, resulting in exposure of the previously shielded adhesion molecules and engagement of the E-selectin-mediated adhesion axis.en
dc.language.isoengen
dc.publisherBioMed Centralen
dc.relation.urlhttp://jeccr.biomedcentral.com/articles/10.1186/s13046-015-0223-9en
dc.titleLoss of the endothelial glycocalyx is associated with increased E-selectin mediated adhesion of lung tumour cells to the brain microvascular endotheliumen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalJournal of experimental & clinical cancer research : CRen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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