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Abstract
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.