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Adenoviral modification of mouse brain derived endothelial cells, bEnd3, to induce apoptosis by vascular endothelial growth factor

Oncogene volume 25, pages 954–958 (2006)Cite this article

Abstract

A second generation genetically-engineered cell-based drug delivery system, referred to as apoptotic-induced drug delivery (AIDD), was developed using endothelial cells (ECs) that undergo apoptosis upon binding of vascular endothelial growth factor (VEGF) to a Flk-1:Fas fusion protein (FF). This new AIDD was redesigned using mouse brain derived ECs, bEnd3 cells, and an adenovirus vector in order to enhance and control the expression of FF. The FF was tagged with a HA epitope (FFHA) and designed to be coexpressed with green fluorescence protein (GFP) by the regulation of cytomegalovirus promoters in the adenovirus vector. bEnd3 cells showed favorable coexpression of FFHA and GFP consistent with the multiplicity of infection of the adenovirus. Immunofluorescence analysis demonstrated that FFHA was localized at the plasma membrane, whereas GFP was predominantly located in the cytoplasm of ECs. Cell death was induced by VEGF, but not by platelet derived growth factor or fibroblast growth factor in a dose-dependent manner (range 2–20 ng/ml), and revealed caspase-dependent apoptotic profiles. The FFHA expressing bEnd3 cells underwent apoptosis when cocultured with a glioma cell (SF188V+) line able to overexpress VEGF. The combined data indicated that the FFHA adenovirus system can induce apoptotic signaling in ECs in response to VEGF, and thus, is an instrumental modification to the development of AIDD.

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Acknowledgements

We thank Drs P Guo, F Zhou and J Ma for technical advice and assistance. This work was supported by NIH Grant CA085577.

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Author notes

  1. Y Mitsuuchi & J M Gallo

    Present address: Professor Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA, 19140, USA

  2. D R Powell

    Present address: Pharmaceutical Development, Centocor Inc., 145 King of Prussia Road, Radnor, PA, 19087, USA

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  1. Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA, USA

    Y Mitsuuchi, D R Powell & J M Gallo

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  1. Y Mitsuuchi
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Correspondence to J M Gallo.

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Mitsuuchi, Y., Powell, D. & Gallo, J. Adenoviral modification of mouse brain derived endothelial cells, bEnd3, to induce apoptosis by vascular endothelial growth factor. Oncogene 25, 954–958 (2006). https://doi.org/10.1038/sj.onc.1209142

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