Opticin exerts its anti-angiogenic activity by regulating extracellular matrix adhesiveness.
Opticin is an extracellular matrix glycoprotein that we identified associated with the collagen network of the vitreous humor of the eye. Recently, we discovered that opticin possesses anti-angiogenic activity using a murine oxygen-induced retinopathy model: here, we investigate the underlying mechanism. Using an ex vivo chick chorioallantoic membrane assay, we show that opticin inhibits angiogenesis when stimulated by a range of growth factors. We show that it suppresses capillary morphogenesis, inhibits endothelial invasion, and promotes capillary network regression in three-dimensional matrices of collagen and Matrigel(TM). We then show that opticin binds to collagen and thereby competitively inhibits endothelial cell interactions with collagen via α(1)β(1) and α(2)β(1) integrins, thereby preventing the strong adhesion that is required for proangiogenic signaling via these integrins.
Medical and Human Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Magali M
MM
Le Goff
Matthew J
MJ
Sutton
Mark
M
Slevin
Ayse
A
Latif
Martin J
MJ
Humphries
Paul N
PN
Bishop
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010100:Oxygen / Q000633:toxicity; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism*; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction
D020533:Angiogenesis Inhibitors; D016326:Extracellular Matrix Proteins; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; C404108:OPTC protein, human; C498607:Optc protein, mouse; D011509:Proteoglycans; D003094:Collagen; D010100:Oxygen