title: Endostatin's heparan sulfate-binding site is essential for inhibition of angiogenesis and enhances in situ binding to capillary-like structures in bone explants.
abstract: The functional role of endostatin's affinity for heparan sulfates was addressed using an ex vivo bone angiogenesis model. Capillary-like sprouts showed prominent expression of collagen XVIII/endostatin. Outgrowth of endothelial cells was not altered in the absence of collagen XVIII but inhibited by the addition of recombinant endostatin. Mutant non-heparan sulfate binding endostatin and the collagen XV endostatin homologue were ineffective. The ability of mutant endostatin to bind to capillary structures was reduced when compared to endostatin. Endostatin-XV completely failed to bind to endothelial cells. Our data indicate that endostatin's angiostatic function is heparan sulfate-dependent, and that in situ-binding of endostatin to endothelial cells is increased by heparan sulfates.
authors.affiliation: Department of Human Genetics, University of Würzburg, Biozentrum, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gaetzner
authors.forename: Martine M L
authors.initials: MM
authors.lastname: Deckers
authors.forename: Sonja
authors.initials: S
authors.lastname: Stahl
authors.forename: Clemens
authors.initials: C
authors.lastname: Löwik
authors.forename: Bjorn R
authors.initials: BR
authors.lastname: Olsen
authors.forename: Ute
authors.initials: U
authors.lastname: Felbor
mesh_terms: D000818:Animals; D001665:Binding Sites; D001846:Bone Development; D001842:Bone and Bones / Q000098:blood supply / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D002478:Cells, Cultured; D043170:Collagen Type XVIII / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D043169:Endostatins / Q000096:biosynthesis / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D051379:Mice; D009154:Mutation; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
chemical_list: D043170:Collagen Type XVIII; D043169:Endostatins; D006497:Heparan Sulfate; D011994:Recombinant Proteins; D012965:Sodium Chloride