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Open Access
Copyright: The authors. This article is an open access
article licensed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0) which permits unrestricted use,
distribution and reproduction in any medium, provided the work is properly
cited.
Research
(Published
online: 02-01-2014)
1. Binding of VEGF-A to canine cancer cells with
preferential expression of VEGFR1 - Antonella Borgatti, Megan Duckett,
Charles Spangler and Jaime F. Modiano
Veterinary World, 7(1): 1-6
doi:
10.14202/vetworld.2014.1-6
Abstract
Aim: Despite encouraging
results in syngeneic and xenografts cancer models with various
inhibitors of vascular endothelial growth factor (VEGF) or its
receptors (VEGFRs), beneficial effects have not been consistently
translated to the clinic, underscoring the need to develop
strategies that go beyond the inhibition of these targets. The
purpose of this study was to generate data to support the
hypothesis that VEGF may be used as “bait” to selectively deliver
therapeutics to VEGFR-expressing cancer cells.
Materials and Methods: VEGFR1 and VEGFR2 expression was
characterized using real time quantitative reverse transcriptase
polymerase chain reaction (RT-qPCR) in canine hemangiosarcoma
(Grace-HSA, Emma-HSA), melanoma (TLM-1), and thyroid
adenocarcinoma (CTAC) cell lines. TLM-1 and Grace-HSA were
identified as representative cell lines that selectively expressed
high levels of VEGFR1. Flow cytometry was performed to examine
binding of a single VEGF molecule (biotinylated VEGFA and avidin
conjugated to fluorescein isothiocyanate (FITC)) by these
chemoresistant cell lines.
Results: RT-qPCR showed that canine tumor cells can
preferentially express VEGFR1 over VEGFR2. Both TLM-1 and Grace-HSA
cell lines, which represent VEGFR1-expressing tumors, showed
specific binding to VEGF-A and this binding was competitively
inhibited by anti-VEGF antibody.
Conclusions: Cells preferentially expressing VEGFR1 can be
targeted with a single VEGF molecule and these ligand-receptor
pairs are well suited for targeting cytotoxic molecules in various
canine tumor cells. Further studies are needed to develop
strategies to selectively deliver therapeutics through VEGF-VEGFRs
binding into VEGFR-expressing tumors.
Keywords: canine, dog, delivery, target, vascular
endothelial growth factor, vascular endothelial growth factor
receptor
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