title: Wnt2 acts as an angiogenic growth factor for non-sinusoidal endothelial cells and inhibits expression of stanniocalcin-1.
abstract: Recently, we have shown that Wnt2 is an autocrine growth and differentiation factor for hepatic sinusoidal endothelial cells. As Wnt signaling has become increasingly important in vascular development and cancer, we analyzed Wnt signaling in non-sinusoidal endothelial cells of different vascular origin (HUVEC, HUAEC, HMVEC-LLy). Upon screening the multiple components of the Wnt pathway, we demonstrated lack of Wnt2 expression, but presence of Frizzled-4, one of its receptors, in cultured non-sinusoidal endothelial cells. Treatment of these cells by exogenous Wnt2 induced endothelial proliferation and sprouting angiogenesis in vitro. Upon analysis of Wnt2 tissue expression as a basis for paracrine Wnt2 effects on non-sinusoidal endothelial cells in vivo, Wnt2 was found to be expressed in densely vascularized murine malignant tumors and in wound healing tissues in close proximity to CD31+ endothelial cells. By gene profiling, stanniocalcin-1 (STC1), a known regulator of angiogenesis, was identified as a target gene of Wnt2 signaling in HUVEC down-regulated by Wnt2 treatment. Tumor-conditioned media counter-acted Wnt2 and up-regulated STC1 expression in HUVEC. In conclusion, we provide evidence that Wnt2 acts as an angiogenic factor for non-sinusoidal endothelium in vitro and in vivo whose target genes undergo complex regulation by the tissue microenvironment.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University Heidelberg, Mannheim, Germany. Diana.Klein.@haut.ma.uni-heidelberg.de
authors.forename: Diana
authors.initials: D
authors.lastname: Klein
authors.forename: Alexandra
authors.initials: A
authors.lastname: Demory
authors.forename: Francis
authors.initials: F
authors.lastname: Peyre
authors.forename: Jens
authors.initials: J
authors.lastname: Kroll
authors.forename: Cyrill
authors.initials: C
authors.lastname: Géraud
authors.forename: Nils
authors.initials: N
authors.lastname: Ohnesorge
authors.forename: Kai
authors.initials: K
authors.lastname: Schledzewski
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051154:Wnt2 Protein / Q000494:pharmacology* / Q000502:physiology
chemical_list: D043925:Angiogenesis Inducing Agents; D006023:Glycoproteins; D051154:Wnt2 Protein; C051795:teleocalcin