Interaction of endostatin with integrins implicated in angiogenesis.
Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show here that recombinantly produced human endostatin interacts with alpha(5)- and alpha(v)-integrins on the surface of human endothelial cells. We further demonstrate that the endostatin-integrin interaction is of functional significance in vitro, as we found that immobilized endostatin supports endothelial cell survival and migration in an integrin-dependent manner. Soluble endostatin in turn inhibits integrin-dependent endothelial cell functions, such as cell migration. Taken together, these results implicate integrins as potential targets for endostatin function and support the importance of integrins in endothelial cell biology and angiogenesis.
Rehn
M
M
Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
Veikkola
T
T
Kukk-Valdre
E
E
Nakamura
H
H
Ilmonen
M
M
Lombardo
C
C
Pihlajaniemi
T
T
Alitalo
K
K
Vuori
K
K
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology*; D043170:Collagen Type XVIII; D004492:Edetic Acid / Q000494:pharmacology; D043169:Endostatins; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D039482:Integrin alpha5; D039564:Integrin alphaV; D007700:Kinetics; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014471:Umbilical Veins
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D043170:Collagen Type XVIII; D043169:Endostatins; D039482:Integrin alpha5; D039564:Integrin alphaV; D009842:Oligopeptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen; D004492:Edetic Acid; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse