A Core Human Primary Tumor Angiogenesis Signature Identifies the Endothelial Orphan Receptor ELTD1 As a Key Regulator of Angiogenesis

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2013 Jul 23

PMID 23871637

Citations 185

Authors

Massimo Masiero

Filipa Costa Simoes

Hee Dong Han

Cameron Snell

Tessa Peterkin

Esther Bridges

Lingegowda S Mangala

Sherry Yen-Yao Wu

Sunila Pradeep

Demin Li

Cheng Han

Heather Dalton

Gabriel Lopez-Berestein

Jurriaan B Tuynman

Neil Mortensen

Ji-Liang Li

Roger Patient

Anil K Sood

Alison H Banham

Adrian L Harris

Francesca M Buffa

Affiliations

Soon will be listed here.

Abstract

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.

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