title: Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis.
abstract: Netrins are secreted molecules with roles in axonal growth and angiogenesis. The Netrin receptor UNC5B is required during embryonic development for vascular patterning, suggesting that it may also contribute to postnatal and pathological angiogenesis. Here we show that unc5b is down-regulated in quiescent adult vasculature, but re-expressed during sprouting angiogenesis in matrigel and tumor implants. Stimulation of UNC5B-expressing neovessels with an agonist (Netrin-1) inhibits sprouting angiogenesis. Genetic loss of function of unc5b reduces Netrin-1-mediated angiogenesis inhibition. Expression of UNC5B full-length receptor also triggers endothelial cell repulsion in response to Netrin-1 in vitro, whereas a truncated UNC5B lacking the intracellular signaling domain fails to induce repulsion. These data show that UNC5B activation inhibits sprouting angiogenesis, thus identifying UNC5B as a potential anti-angiogenic target.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U833, F-75005 Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Larrivée
authors.forename: Catarina
authors.initials: C
authors.lastname: Freitas
authors.forename: Marc
authors.initials: M
authors.lastname: Trombe
authors.forename: Xiang
authors.initials: X
authors.lastname: Lv
authors.forename: Benjamin
authors.initials: B
authors.lastname: Delafarge
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.forename: Karine
authors.initials: K
authors.lastname: Bouvrée
authors.forename: Christiane
authors.initials: C
authors.lastname: Bréant
authors.forename: Raquel
authors.initials: R
authors.lastname: Del Toro
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bréchot
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain
authors.forename: Françoise
authors.initials: F
authors.lastname: Bono
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dol
authors.forename: Filip
authors.initials: F
authors.lastname: Claes
authors.forename: Christian
authors.initials: C
authors.lastname: Fischer
authors.forename: Monica
authors.initials: M
authors.lastname: Autiero
authors.forename: Jean-Léon
authors.initials: JL
authors.lastname: Thomas
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Anne
authors.initials: A
authors.lastname: Eichmann
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D011509:Proteoglycans / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects; D051381:Rats; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D007797:Laminin; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C059485:matrigel; D000075388:Netrin-1; D003094:Collagen