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.