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U. Ozerdem; Targeting Neovascular Pericytes in Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4620.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine whether interference with the function of a pericyte component, the NG2 proteoglycan, inhibits neovascularization in uveal melanoma. To determine the details of temporal and spatial relationship between pericytes (PC) and endothelial cells (EC) in angiogenic sprouts in uveal melanoma. Methods: Orthotopic human choroidal and ciliary body melanoma (OCM–1A) xenografts were induced in cyclosporin A–immunosuppressed NG2 knockout and wild type mice. The eyes were enucleated 2 weeks after tumor inoculation. Immunohistochemical staining combined with confocal microscopy (Fluoview 1000), and image analysis (Volocity software) were used to investigate the PC–EC relationship and microvascular density (MVD). Endothelial cells were identified using a cocktail of antibodies against endoglin (CD105), PECAM–1 (CD31), and VEGF receptor–2 (flk–1). Pericytes were identified by labeling with antibodies against the NG2 proteoglycan and PDGF beta–receptor. Results: All eyes developed tumors. Inoculated OCM–1A tumor cells showed NG2 expression both in NG2 knockout and wild type mice. NG2–negative and PDGF beta receptor–positive pericytes in NG2 knockout mice, and NG2–positive and PDGF beta receptor–positive pericytes in the wild type mice invest continuously endothelial walls and sprouts. Pericyte tubes (i.e. vascular channels formed solely by pericytes lacking endothelial cells) were also identified. Mean microvascular density (MVD) in NG2 knockout eyes was 43.7% lower than wild type controls (n= 18 eyes, p=0.0166, Mann–Whitney test). Conclusions: Contribution of pericytes to angiogenic vessels in uveal melanoma is extensive. Nascent pericytes in uveal melanoma derive from the host tissue. Inhibition of pericytes through a key pericyte component, NG2 proteoglycan, decreases neovascularization. Therefore, pericytes and NG2 proteoglycan are potential cellular and molecular therapeutic targets in uveal melanoma.
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