CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion

Jennifer E. Totonchy, Lisa Clepper, Kevin G. Phillips, Owen McCarty, Ashlee Moses

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)165-176
Number of pages12
JournalCell Adhesion and Migration
Volume8
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Homeostasis
Endothelial Cells
Ligands
Blood Vessels
CD31 Antigens
Contact Inhibition
Physiological Phenomena
Neoplasms
Wound Healing
Immunity

Keywords

  • Cancer vascular dysfunction
  • CXCR7
  • ECIS
  • Endothelial cell adhesion
  • Invasion
  • PECAM-1

ASJC Scopus subject areas

  • Cell Biology
  • Cellular and Molecular Neuroscience

Cite this

CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion. / Totonchy, Jennifer E.; Clepper, Lisa; Phillips, Kevin G.; McCarty, Owen; Moses, Ashlee.

In: Cell Adhesion and Migration, Vol. 8, No. 2, 2014, p. 165-176.

Research output: Contribution to journalArticle

Totonchy, Jennifer E. ; Clepper, Lisa ; Phillips, Kevin G. ; McCarty, Owen ; Moses, Ashlee. / CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion. In: Cell Adhesion and Migration. 2014 ; Vol. 8, No. 2. pp. 165-176.
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