Binding of VEGF-A to canine cancer cells with preferential expression of VEGFR1

Antonella Borgatti, Megan Duckett, Spangler Charles, Jaime F. Modiano

Research output: Contribution to journalArticle

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 VEGFRexpressing 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-HSAwere 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 ligandreceptor 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.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalVeterinary World
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2014

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vascular endothelial growth factor A
vascular endothelial growth factors
Vascular Endothelial Growth Factor A
Canidae
dogs
cell lines
Neoplasms
receptors
neoplasms
Cell Line
reverse transcriptase polymerase chain reaction
Reverse Transcriptase Polymerase Chain Reaction
hemangiosarcoma
therapeutics
avidin
isothiocyanates
fluorescein
melanoma
adenocarcinoma
baits

Keywords

  • Canine
  • Delivery
  • Dog
  • Target
  • Vascular endothelial growth factor
  • Vascular endothelial growth factor receptor

Cite this

Binding of VEGF-A to canine cancer cells with preferential expression of VEGFR1. / Borgatti, Antonella; Duckett, Megan; Charles, Spangler; Modiano, Jaime F.

In: Veterinary World, Vol. 7, No. 1, 01.01.2014, p. 1-6.

Research output: Contribution to journalArticle

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