Soluble N-cadherin fragment promotes angiogenesis.
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.
Derycke
L
L
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Gent, Belgium. lara.derycke@ugent.be
Morbidelli
L
L
Ziche
M
M
De Wever
O
O
Bracke
M
M
Van Aken
E
E
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
D015820:Cadherins; D017468:Receptors, Fibroblast Growth Factor