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 language | English (US) |
|---|---|
| Article number | e69828 |
| Journal | PLoS One |
| Volume | 8 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 23 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Aberrant Proliferation in CXCR7+ Endothelial Cells via Degradation of the Retinoblastoma Protein
AU - Totonchy, Jennifer E.
AU - Osborn, Jessica M.
AU - Botto, Sara
AU - Clepper, Lisa
AU - Moses, Ashlee
PY - 2013/7/23
Y1 - 2013/7/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84880743712&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880743712&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0069828
DO - 10.1371/journal.pone.0069828
M3 - Article
C2 - 23894550
AN - SCOPUS:84880743712
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e69828
ER -