Targeting Olfactomedin-like 3 Inhibits Tumor Growth by Impairing Angiogenesis and Pericyte Coverage
Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en ciblant deux types cellulaires du micro-environnement tumoral, des anticorps anti-Olfml3 ont une activité anti-angiogénique
Anti-angiogenic drugs have been used as anti-cancer agents to target tumor endothelial cells or pericytes. Due to limited efficacy of the current mono-therapies, there is a strong demand for dual targeting of endothelial cells and pericytes. Here, we identify Olfactomedin-like 3 (Olfml3) as a novel pro-angiogenic cue within the tumor microenvironment. Tumor-derived Olfml3 is produced by both tumor endothelial cells and accompanying pericytes and deposited in the peri-vascular compartment. Blockade of Olfml3 by anti-Olfml3 antibodies is highly effective in reducing tumor vascularization, pericyte coverage and tumor growth. In vitro, Olfml3 targeting is sufficient to inhibit endothelioma cell migration and sprouting. Olfml3 alone or through binding to BMP4 enhances the canonical SMAD1/5/8 signaling pathway required for BMP4-induced angiogenesis. Therefore, Olfml3 blockade provides a novel strategy to control tumor growth by targeting two distinct cell types within the tumor microenvironment using a single molecule.
http://mct.aacrjournals.org/content/early/2012/09/20/1535-7163.MCT-12-0245.abstract