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Title

Targeting Olfactomedin-like 3 Inhibits Tumor Growth by Impairing Angiogenesis and Pericyte Coverage
Authors
Miljkovic-Licina, Marijana
Hammel, Philippe
Garrido-Urbani, Sarah
Lee, Boris
Meguenani, Mehdi
Chaabane, Chiraz
Bochaton-Piallat, Marie-Luce
Imhof, Beat
Published in Molecular cancer therapeutics. 2012, vol. 11, no. 12, p. 2588-99
Abstract 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.
Identifiers
PMID: 23002094
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Structures
Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group Bochaton-Piallat Marie-Luce (pathologie et immunologie) (646)
Citation
(ISO format) 		MILJKOVIC-LICINA, Marijana et al. Targeting Olfactomedin-like 3 Inhibits Tumor Growth by Impairing Angiogenesis and Pericyte Coverage. In: Molecular cancer therapeutics, 2012, vol. 11, n° 12, p. 2588-99. doi: 10.1158/1535-7163.MCT-12-0245 https://archive-ouverte.unige.ch/unige:27947

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Deposited on : 2013-05-21

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