%A Lejmi, Esma %A Bouras, Ilyes %A Camelo, Serge %A Roumieux, Marie %A Minet, Norbert %A Leré-Déan, Carole %A Merkulova-Rainon, Tatyana %A Autret, Gwennhael %A Vayssettes, Catherine %A Clement, Olivier %A Plouët, Jean %A Leconte, Laurence %D 2014 %T Netrin-4 promotes mural cell adhesion and recruitment to endothelial cells %K %X Abstract   Netrins are secreted molecules involved in axon guidance and angiogenesis. We previously showed that Netrin-4 acts as an anti-angiogenic factor by inhibiting endothelial cell (EC) functions. In this study, we investigated the effects of Netrin-4 on vascular smooth muscle cell (VSMC) activity in vitroand in vivo. We show that exogenous Netrin-4 stimulated VSMC adhesion and migration, and increased their coverage on EC tubes (grown on a Matrigel substrate). siRNA knock-down of endogenous Netrin-4 expression in VSMC decreased their recruitment to EC tubes. VSMC expressed Netrin-4 and three of the six Netrin-1 cognate receptors: DCC, Neogenin, and Unc5B. Silencing of these receptors reduced Netrin-4 adhesion to VSMC, strongly suggesting that these receptors were involved in the recruitment process. We previously showed that Netrin-4 overexpression in PC3 cancer cells delayed tumor growth in a model of subcutaneous xenograft by reducing tumor vessel density. Here, we show that Netrin-4 overexpression improved tumor blood vessel structure and increased VSMC coverage. Thus, Netrin-4 induced mural cell recruitment may play a role in the inhibition of tumor growth. Our data suggest that Netrin-4 is important for blood vessel normalization through the regulation of both endothelial and perivascular cells. %U https://vascularcell.com/index.php/vc/article/view/10.1186-2045-824X-6-1 %J Vascular Cell %0 Journal Article %R 10.1186/2045-824X-6-1 %P 1%V 6 %N 1 %@ 2045-824X %8 2014-01-28