title: Oncothanin, a peptide from the alpha3 chain of type IV collagen, modifies endothelial cell function and inhibits angiogenesis.
abstract: Previous studies from our group and the group of the Department of Biochemistry at the University of Rheims, France [corrected] have shown that basement membrane (BM) collagen from anterior lens capsule type IV collagen (ALC-COL IV) and peptides from the noncollagenous domain (NC1) of the alpha3(IV) [corrected] chain, corresponding to residues 185-203 and 179-208, inhibit tumor cell proliferation, specifically through the interaction of the -SNS- tripeptide (residues 189-191) with the CD47/alphavbeta3 integrin receptor complex. Data presented here demonstrate that the alpha3(IV)185-203 and the alpha3(IV)179-208 peptides, from here forward [corrected] designated as oncothanin, regulate endothelial cell (EC) proliferation, adhesion, and motility which [corrected] ultimately influence angiogenesis. The data also indicate that oncothanin, when used as a chemoattractant, greatly enhanced EC chemotaxis. In contrast, pretreatment of EC with oncothanin inhibited chemotaxis toward several different chemoattractants. When oncothanin was used as a substrate, it enhanced EC adhesion that was inhibited when pretreated with same. Analysis of angiogenesis by EC differentiation (tube formation), aortic ring microvessel formation [corrected] and the chorioallantoic membrane assay, [corrected] demonstrate that oncothanin, but not the control medium or peptides, inhibits angiogenesis. In the EC differentiation assay, oncothanin completely inhibited tube formation at 25 microg/ml, whereas peptides with comparable sequences, that lacked [corrected] the -SNS- sequence, from ALC-COL IV NC1 domains alpha1 and alpha2 chains failed to inhibit tube formation. The data support the hypothesis that ALC-COL IV and oncothanin inhibit angiogenesis by modulation of EC function.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Shahan
authors.forename: Derrick
authors.initials: D
authors.lastname: Grant
authors.forename: Mason
authors.initials: M
authors.lastname: Tootell
authors.forename: Zahra
authors.initials: Z
authors.lastname: Ziaie
authors.forename: Nobuko
authors.initials: N
authors.lastname: Ohno
authors.forename: Shaker
authors.initials: S
authors.lastname: Mousa
authors.forename: Siema
authors.initials: S
authors.lastname: Mohamad
authors.forename: Horace
authors.initials: H
authors.lastname: Delisser
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kefalides
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects; D051928:CD47 Antigen; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D024141:Collagen Type IV / Q000737:chemistry*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D024141:Collagen Type IV; D039302:Integrin alphaVbeta3; D010446:Peptide Fragments