Targeting pericytes diminishes neovascularization in orthotopic uveal melanoma in nerve/glial antigen 2 proteoglycan knockout mouse.
In this investigation, we explored whether knockout of nerve/glial antigen 2 (NG2), a pericyte component, inhibited neovascularization and growth of uveal melanoma xenografts. For this, we used multichannel laser scanning confocal microscopy and quantitative image analysis. Orthotopic human uveal melanoma (OCM-1A) xenografts were induced in NG2 knockout and wild-type mice, which were immunosuppressed with cyclosporin A. Inhibition of pericytes through NG2 proteoglycan decreased neovascularization and tumor end volume, rendering pericytes and NG2 proteoglycan potential cellular and molecular therapeutic targets in uveal melanoma.
Ozerdem
Ugur
U
La Jolla Institute for Molecular Medicine, San Diego, Calif, USA. ozerdem@ljimm.org
D000818:Animals; D000941:Antigens / Q000502:physiology*; D015703:Antigens, CD / Q000378:metabolism; D000071063:Endoglin; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020286:Pericytes / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011509:Proteoglycans / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014604:Uveal Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D015703:Antigens, CD; D000071063:Endoglin; D005904:Glial Fibrillary Acidic Protein; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D011956:Receptors, Cell Surface; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099216:Chondroitin Sulfate Proteoglycan 4; C064206:ENG protein, human