(447f) Endothelial Glycocalyx Degradation in Disturbed Flow Enhances the Attachment of MCF7 Breast Cancer Cells Attachment to the Endothelium

Authors: 
Nersesyan, A., Northeastern University
Mensah, S., Northeastern University
Enright, M., Northeastern University
Niedre, M., Northeastern University
Ebong, E. E., Northeastern University
The endothelial glycocalyx (GCX), a sugar-rich layer lining of the luminal surface of the endothelium, provides barrier protection against vascular invasion of circulating cells and molecules in the blood. The presence of a tumor burden triggers a cascade of events that drive vascular tissue damage, endothelial cell activation, and recruitment of circulating tumor cells (CTCs) to sites of secondary tumor formation. E-selectin is recognized as a mediator of cancer cell adhesion and is an adhesion molecule that is expressed in the events of endothelial cell activation. Arrest of the CTCs from the blood flow may be mediated by the interactions between CTCs and E-selectin that is embedded in the GCX layer of the endothelial cells. We hypothesize that E-selectin becomes accessible to CTCs due degradation of the flow-regulated GCX. Vessel bifurcations and clinical interventions create changes in vessel geometry that affect the flow of blood and initiates endothelial cell GCX restructuring. Therefore, we also hypothesize that dynamic blood flow patterns in areas of vascular bifurcations will cause a reduction in the coverage and thickness of GCX which will in turn result in the exposure of E-selectin and increased rate of cancer attachment, clustering of cancer cells, and also increased migration of cancer cell across the endothelial layer. To test our hypotheses, we used a customized parallel plate flow chamber that introduces disturbed flow patterns to human umbilical vein endothelial cells (HUVEC) alongside with immunostaining and confocal microscopy. We showed that on HUVEC exposed to disturbed flow conditions the GCX coverage and thickness are reduced significantly in comparison with uniform flow conditions. These GCX changes correlate to increase in the exposure of E-Selectin and a significant loss of endothelial barrier function, which in turn causes an increase in the adhesion rate of MCF-7 human breast cancer cells to the endothelium.