Document Type
Article
Publication Date
2014
Abstract
The homeostatic function of endothelial cells (EC ) is critical for a number of physiological processes including vascular integrity, immunity, and wound healing. Indeed, vascular abnormalities resulting from EC dysfunction contribute to the development and spread of malignancies. The alternative SDF-1/CXCL12 receptor CXCR7 is frequently and specifically highly expressed in tumor-associated vessels. In this study, we investigate whether CXCR7 contributes to vascular dysfunction by specifically examining the effect of CXCR7 expression on EC barrier function and motility. We demonstrate that CXCR7 expression in EC results in redistribution of CD31/PECAM-1 and loss of contact inhibition. Moreover, CXCR7+ EC are deficient in barrier formation. We show that CXCR7-mediated motility has no influence on angiogenesis but contributes to another motile process, the invasion of CXCR7+ EC into ligand-rich niches. These results identify CXCR7 as a novel manipulator of EC barrier function via alteration of PECAM-1 homophilic junctions. As such, aberrant expression of CXCR7 in the vasculature has the potential to disrupt vascular homeostasis and could contribute to vascular dysfunction in cancer systems.
Recommended Citation
Totonchy JE, Clepper L, Phillips KG, McCarty OJ, Moses AV. CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion. Cell Adh Migr. 2014;8(2):165-176. doi:10.4161/cam.28495.
Copyright
Taylor & Francis
Included in
Amino Acids, Peptides, and Proteins Commons, Complex Mixtures Commons, Hemic and Immune Systems Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Virus Diseases Commons
Comments
This is an Accepted Manuscript of an article published in Cell Adhesion & Migration, volume 8, issue 2, in 2014, available online: http://www.tandfonline.com/10.4161/cam.28495. It may differ slightly from the final version of record.