Aberrant Proliferation in CXCR7+ Endothelial Cells via Degradation of the Retinoblastoma Protein

Jennifer E. Totonchy, Jessica M. Osborn, Sara Botto, Lisa Clepper, Ashlee Moses

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor suppressor protein Rb. These findings identify a heretofore unappreciated role for CXCR7 in vascular dysfunction and confirm this receptor as a plausible target for anti-tumor therapy.

Original languageEnglish (US)
Article numbere69828
JournalPLoS One
Volume8
Issue number7
DOIs
StatePublished - Jul 23 2013

Fingerprint

Retinoblastoma Protein
Endothelial cells
protein degradation
endothelial cells
Tumors
Endothelial Cells
Degradation
neoplasms
Neoplasms
blood vessels
Blood Vessels
Tumor Suppressor Proteins
Cell proliferation
angiogenesis
endothelium
Cell culture
growth factors
cell proliferation
cell culture
Endothelium

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Aberrant Proliferation in CXCR7+ Endothelial Cells via Degradation of the Retinoblastoma Protein. / Totonchy, Jennifer E.; Osborn, Jessica M.; Botto, Sara; Clepper, Lisa; Moses, Ashlee.

In: PLoS One, Vol. 8, No. 7, e69828, 23.07.2013.

Research output: Contribution to journalArticle

Totonchy, Jennifer E. ; Osborn, Jessica M. ; Botto, Sara ; Clepper, Lisa ; Moses, Ashlee. / Aberrant Proliferation in CXCR7+ Endothelial Cells via Degradation of the Retinoblastoma Protein. In: PLoS One. 2013 ; Vol. 8, No. 7.
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