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  1. N Gutowski1,2,
  2. S Rai2,
  3. J Whatmore2
  1. 1Royal Devon and Exeter Hospital
  2. 2University of Exeter Medical School


Metastatic lung cancer cell arrest along brain microvasculature maybe mediated by interactions between ligands on circulating tumour cells and E-selectin adhesion molecules on brain endothelial cells, which are shielded by a dense endothelial glycocalyx layer. We previously identified proteins, including vascular endothelial growth factor (VEGF) and tumour necrosis factor-alpha (TNF-α), in A549 and SK-MES-1 lung tumour conditioned media, which enhance tumour cell adhesion to human brain microvascular endothelial cells (HBMECs).

Aim To examine whether increased lung tumour/HBMEC adhesion is a consequence of VEGF and TNF-α-induced brain endothelial glycocalyx degradation subsequently enhancing E-selectin exposure.

Methods Following treatment with 0.2 ng/ml VEGF and 160 pg/ml TNF-α, endothelial glycocalyx changes were measured by binding of fluorescein isothiocyanate-linked wheat germ agglutinin (WGA-FITC). E-selectin levels were quantified by ELISA.

Results Both VEGF and TNF-α significantly reduced WGA-FITC staining of HBMEC glycocalyx by more than 20% to 74±5.2% and 77±3.8%, respectively compared to control (100%) (p≤0.05, n=6). After 30mins, enhanced E-selectin levels were also observed (VEGF: 146±41.0% and TNF-α: 122±11.2%) (p=0.037, n=3).

Conclusion Lung tumour cell secreted VEGF and TNF-α enhance lung tumour cell adhesion to HBMECs by inducing endothelial glycocalyx degradation revealing previously ‘hidden’ E-selectin.

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