Oncothanin, a peptide from the alpha3 chain of type IV collagen, modifies endothelial cell function and inhibits angiogenesis.
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.
Shahan
Tracy
T
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Grant
Derrick
D
Tootell
Mason
M
Ziaie
Zahra
Z
Ohno
Nobuko
N
Mousa
Shaker
S
Mohamad
Siema
S
Delisser
Horace
H
Kefalides
Nicholas
N
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
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D024141:Collagen Type IV; D039302:Integrin alphaVbeta3; D010446:Peptide Fragments