title: Aberrant proliferation in CXCR7+ endothelial cells via degradation of the retinoblastoma protein.
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.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Totonchy
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Osborn
authors.forename: Sara
authors.initials: S
authors.lastname: Botto
authors.forename: Lisa
authors.initials: L
authors.lastname: Clepper
authors.forename: Ashlee V
authors.initials: AV
authors.lastname: Moses
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D040081:Protein Array Analysis; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: C501896:ACKR3 protein, human; D008024:Ligands; D054387:Receptors, CXCR; D016160:Retinoblastoma Protein; D046988:Proteasome Endopeptidase Complex
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