Adeno-associated virus vector-mediated delivery of pigment epithelium-derived factor restricts neuroblastoma angiogenesis and growth
Section snippets
Cell lines
The human NB cell line NB-1691, provided by Dr P. Houghton (Memphis, Tenn), the murine NB cell line NXS2, provided by Dr R. Reisfeld (La Jolla, Calif), and the 293T cells (human embryonic kidney cells expressing SV40 large T antigen, American Type Culture Collection, Manassas, Va) were used in this study.
Inhibition of in vitro endothelial cell activation and tubule formation
Vascular endothelial growth factor (VEGF)–stimulated endothelial cell proliferation and basic fibroblast growth factor (bFGF)-stimulated endothelial cell migration and tubule formation assays
In vitro assessment of PEDF expression and function
Functional assessment of PEDF generated from the AAV PEDF vector was performed first. Conditioned medium from transfected cells was collected, and its ability to inhibit endothelial cell activation in vitro was assessed. Medium from cells expressing PEDF was able to inhibit bFGF-stimulated endothelial cell migration and VEGF-stimulated proliferation. As shown in Fig. 1A, a 34% decrease in endothelial cell migration and 35% decrease in endothelial cell proliferation were seen as compared with
Discussion
Adeno-associated virus vectors have several properties making them particularly promising vectors for gene therapy [7]. Importantly, rAAV has been shown to direct long-term transgene expression from nondividing cells in vivo [8], [26], [27]. Furthermore, AAV has an excellent safety profile, evokes little immune response because genes encoding wild-type protein are absent, is naturally replication-deficient, and is not known to be associated with any human disease. In recent studies, we have
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PEDF is an endogenous inhibitor of VEGF-R2 angiogenesis signaling in endothelial cells
2021, Experimental Eye ResearchCitation Excerpt :For example, increased levels of VEGF and decreased levels of PEDF are evident in the vitreous of patients with proliferative diabetic retinopathy, age related macular degeneration, and retinal detachment (Bhutto et al., 2006; Cheung et al., 2006; Mohan et al., 2012; Ogata et al., 2002; Ohno-Matsui et al., 2001). The relative levels of VEGF-A and PEDF are also good indicators of the status and prognosis of tumor progression and metastasis (Abramson et al., 2003; Becerra and Notario, 2013; Cheung et al., 2006; Guan et al., 2004; Rivera-Pérez et al., 2018; Streck et al., 2005). In many tumors decreased PEDF levels alter the ratio in favor of tumor growth, whereas addition of exogenous PEDF leads to reduced tumor proliferation and tumor angiogenesis.
The increasing role of pigment epithelium-derived factor in metastasis: from biological importance to a promising target
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2013, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :In the present study, we have further studied the relation between PEDF and microvessel density and have demonstrated a negative correlation in PEDF expression and angiogenesis of bladder cancers. The result is concordant with that in researches involving glioma [19], neuroblastoma [20], and prostate cancer [7]. Nonetheless, it is still unclear how distinctive factors interact in the antiangiogenic pathway PEDF mediates [18], and we have thus involved another potent proangiogenic factor, TNF-α, aiming for identifying whether the element functions in middle of the complicated pathway.