title: Soluble N-cadherin fragment promotes angiogenesis.
abstract: Endothelial cells express two dependent intercellular adhesion molecules: vascular endothelial (VE)-cadherin, specific for endothelial cells, and N-cadherin, also present in neuronal, lens, skeletal and heart muscle cells, osteoblasts, pericytes and fibroblasts. While there exists a vast amount of evidence that VE-cadherin promotes angiogenesis, the role of N-cadherin still remains to be elucidated. We found that a soluble 90-kDa fragment N-cadherin promotes angiogenesis in the rabbit cornea assay and in the chorioallantoic assay when cleaved enzymatically from the extracellular domain of N-cadherin. Soluble N-cadherin stimulates migration of endothelial cells in the wound healing assay and stimulates phosphorylation of extracellular regulated kinase. In vitro experiments with PD173074 and knock-down of N-cadherin and fibroblast growth factor (FGF)-receptor, showed that the pro-angiogenic effect of soluble N-cadherin is N-cadherin- and FGF-receptor-dependent. Our results suggest that soluble N-cadherin stimulates migration of endothelial cells through the FGF-receptor.
authors.affiliation: Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Gent, Belgium. lara.derycke@ugent.be
authors.forename: L
authors.initials: L
authors.lastname: Derycke
authors.forename: L
authors.initials: L
authors.lastname: Morbidelli
authors.forename: M
authors.initials: M
authors.lastname: Ziche
authors.forename: O
authors.initials: O
authors.lastname: De Wever
authors.forename: M
authors.initials: M
authors.lastname: Bracke
authors.forename: E
authors.initials: E
authors.lastname: Van Aken
mesh_terms: D000818:Animals; D015820:Cadherins / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003315:Cornea / Q000098:blood supply; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation; D011817:Rabbits; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D013997:Time Factors; D014945:Wound Healing
chemical_list: D015820:Cadherins; D017468:Receptors, Fibroblast Growth Factor