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A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer

A Corrigendum to this article was published on 14 March 2007

Abstract

Different antiangiogenic and antimetastatic recombinant adenoviruses were tested in a transgenic mouse model of metastatic ocular cancer (TRP1/SV40 Tag transgenic mice), which is a highly aggressive tumor, developed from the pigmented epithelium of the retina. These vectors, encoding amino-terminal fragments of urokinase plasminogen activator (ATF), angiostatin Kringles (K1–3), endostatin (ES) and canstatin (Can) coupled to human serum albumin (HSA) were injected to assess their metastatic and antiangiogenic activities in our model. Compared to AdCO1 control group, AdATF-HSA did not significantly reduce metastatic growth. In contrast, mice treated with AdK1–3-HSA, AdES-HSA and AdCan-HSA displayed significantly smaller metastases (1.19±1.19, 0.87±1.5, 0.43±0.56 vs controls 4.04±5.12 mm3). Moreover, a stronger inhibition of metastatic growth was obtained with AdCan-HSA than with AdK1–3-HSA (P=0.04). Median survival was improved by 4 weeks. A close correlation was observed between the effects of these viruses on metastatic growth and their capacity to inhibit tumor angiogenesis. Our study indicates that systemic antiangiogenic factors production by recombinant adenoviruses, particularly Can, might represent an effective way of delaying metastatic growth via inhibition of angiogenesis.

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Acknowledgements

We are very grateful to all the staff (in particular C Chianale and P Ardouin) in the animal facilities at the Institut Gustave Roussy for their help during the in vivo experiments. We thank Faroudy Boufassa (INSERM CHU de Bicêtre) for his help in statistical analysis. We also thank L St Ange for editing. La Ligue National Contre le Cancer, l'Association pour la Recherche Contre le Cancer (ARC), and le Centre National de la Recherche scientifique (CNRS) are acknowledged for financial support.

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Correspondence to C Bouquet.

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Frau, E., Magnon, C., Opolon, P. et al. A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer. Cancer Gene Ther 14, 251–261 (2007). https://doi.org/10.1038/sj.cgt.7701005

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  • DOI: https://doi.org/10.1038/sj.cgt.7701005

Keywords

  • antiangiogenic factors
  • HSA conjugates
  • metastasis
  • transgenic mice

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