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William Coppess, Zachary K. Goldsmith, Madison Ritter, Kelley Yuan, Andrew S Irvine, Rachel Brennan, Matthew W Wilson, Vanessa Marie Morales; The impact of disruption of PDGF-PDGFR-β signaling on VEGF-VEGFR signaling in retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1780.
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© ARVO (1962-2015); The Authors (2016-present)
Retinoblastoma (Rb) is a common intraocular malignancy in children. Targeting of tumor vasculature is important to disrupt the growth and nourishment of tumors. Vascular endothelial growth factor (VEGF) is considered a major regulator in retinal angiogenesis. However, recent work suggests VEGF is important in neural development. Previously, we showed disruption of PDGFR-β signaling reduces Rb proliferation and invasion. Here, we investigate if there is a compensatory mechanism by VEGFR2 in the absence of PDGFR-β signaling.
We used Y79, the metastatic model of Rb, to investigate the expression and upregulation of VEGF-VEGFR2 signaling after disruption of the PDGFR-β downstream signaling. We measured VEGFA, VEGFR2 mRNA by qPCR analyses and protein levels by Western blot. We also measured the expression of these molecules by qPCR using samples from an orthotopic xenograft system.
qPCR analyses showed upregulation of the VEGFR2 and VEGFA in Rb cell cultures and in the ocular tissue from an orthotopic xenograft system. When the PDGF-PDGFR-β downstream signaling was disrupted, there was no change in the VEGFR2 signaling, measured by the ratio of phosphorylated to total VEGFR2.
Our results showed no changes in VEGFR signaling in Y79 Rb cells after disruption of the PDGF-PDGFR-β signaling pathway. These results suggest there is no compensatory mechanism by VEGFR2 in the absence of signaling through PDGF-PDGFR-β. Modulation of PDGFR-β affects angiogenesis, but does not affect VEGF-VEGFR, which may play a role in neural development.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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