A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis. Cancer Cell 2013 Aug 12;24(2):229-41
Date
07/23/2013Pubmed ID
23871637Pubmed Central ID
PMC3743050DOI
10.1016/j.ccr.2013.06.004Scopus ID
2-s2.0-84881549640 (requires institutional sign-in at Scopus site) 216 CitationsAbstract
Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumor-associated endothelial cells, with a higher expression correlating with favorable prognosis. Importantly, ELTD1 silencing impairs endothelial sprouting and vessel formation in vitro and in vivo, drastically reducing tumor growth and greatly improving survival. Collectively, these results provide insight into the regulation of tumor angiogenesis and highlight ELTD1 as key player in blood vessel formation.
Author List
Masiero M, Simões FC, Han HD, Snell C, Peterkin T, Bridges E, Mangala LS, Wu SY, Pradeep S, Li D, Han C, Dalton H, Lopez-Berestein G, Tuynman JB, Mortensen N, Li JL, Patient R, Sood AK, Banham AH, Harris AL, Buffa FMAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Growth Processes
Endothelial Cells
Female
Genetic Predisposition to Disease
HCT116 Cells
Humans
Mice
Mice, Nude
Neoplasms
Neovascularization, Pathologic
Receptors, G-Protein-Coupled
Signal Transduction
