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Role of cell surface molecules and autologous ascitic fluid in determining efficiency of adenoviral transduction of ovarian cancer cells

Cancer Gene Therapy volume 17, pages 684–693 (2010)Cite this article

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Abstract

Adenovirus is the most frequently used virus in gene therapy clinical trials. There have been conflicting reports on the ability of adenovirus to transduce primary ovarian cancer samples and the expression of relevant cell surface molecules. These factors were examined using primary ovarian cancer cells cultured from ascites and solid tumor to gain insights into the clinical use of adenovirus in ovarian cancer. The level of transduction of primary cultures was much higher than uncultured cells and established cell lines, and correlated with higher levels of coxsackie-adenovirus receptor (CAR) and integrin expression. Growth of primary cultures in autologous ascitic fluid prevented an increase in CAR expression and inhibited transduction compared with cells treated in supplemented RPMI. Cells at the periphery of solid tumor samples were transduced using a replication-incompetent virus and correlated with CAR expression. However, transduction was abolished by autologous ascitic fluid, despite the expression of CAR. We conclude that the use of adenoviruses for ovarian cancer gene therapy will require testing in the presence of inhibitory factors in ascitic fluid. The clinical use of adenoviral vectors may require circumvention of such inhibitory factors and the use of replication competent adenovirus to enable efficient viral penetration of the cancer.

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Abbreviations

EOC:

epithelial ovarian cancer

CK:

cytokeratin

CAR:

coxsackie-adenovirus receptor

GFP:

green fluorescent protein

BSA:

bovine serum albumin

MFI:

median fluorescent intensity

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Acknowledgements

We thank Nick Griffin and Nafisa Wilkinson for pathological examination of samples, Paul Roberts from Clinical Cytogenetics at St James's Hospital for preparing and examining metaphase spreads of the primary cells for malignancy, and Filomena Estefez from Leeds Institute of Molecular Medicine for the CAR immunohistochemisty and Alaa Elghobashy for providing the solid tumor samples. This work was funded by Cancer Research UK.

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Authors and Affiliations

  1. Department of Oncology, Cancer Research UK Clinical Centre in Leeds, St James's University Hospital, Leeds, UK

    N Ingram, L P MacCormac, N T Oxley & G D Hall

  2. Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK

    P A Burns

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Correspondence to N Ingram.

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Ingram, N., MacCormac, L., Oxley, N. et al. Role of cell surface molecules and autologous ascitic fluid in determining efficiency of adenoviral transduction of ovarian cancer cells. Cancer Gene Ther 17, 684–693 (2010). https://doi.org/10.1038/cgt.2010.24

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