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The roles of cell surface attachment molecules and coagulation Factor X in adenovirus 5-mediated gene transfer in pancreatic cancer cells

Cancer Gene Therapy volume 18, pages 478–488 (2011)Cite this article

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Abstract

Transduction of 11 pancreatic cancer cell lines with a replication-deficient adenovirus 5 expressing enhanced green fluorescent protein (Ad5EGFP) was analyzed and variable EGFP levels were observed, ranging from <1% to ∼40% of cells transduced, depending on the cell line. Efficient Ad5EGFP transduction was associated mainly with higher levels of cell surface Coxsackie and adenovirus receptor (CAR) but not with expression of αvβ3 and αvβ5 integrins and was fiber dependent. Reduction of CAR by RNA interference resulted in a corresponding decrease in Ad5EGFP transduction. Pre-treatment of Ad5EGFP with blood coagulation Factor X increased virus entry even in the presence of low CAR levels generated by RNA interference, suggesting a potential alternative route of Ad5 entry into pancreatic cancer cells. Immunohistochemistry carried out on 188 pancreatic ductal adenocarcinomas and 68 matched controls showed that CAR was absent in 102 (54%) of adenocarcinomas, whereas moderate and strong staining was observed in 58 (31%) and 28 (15%) cases, respectively. Weak or absent CAR immunolabeling correlated with poor histological differentiation of pancreatic cancer. In normal tissue, strong immunolabeling was detected in islet cells and in the majority of inter- and intralobular pancreatic ducts.

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Abbreviations

Ad:

human adenovirus

CAR:

Coxsackie and adenovirus receptor

EGFP:

enhanced green fluorescent protein

FX:

Factor X

vp:

virus particles

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Acknowledgements

We thank Yorkshire Cancer Research and the Government of Malaysia for financial support and Maria Blair Zajdel for comments and advice.

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Author notes

  1. S Hamdan, C S Verbeke and N Fox: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK

    S Hamdan, N Fox, G Bottley & G E Blair

  2. Department of Histopathology, St James's University Hospital, Leeds, UK

    C S Verbeke & J Booth

  3. Postgraduate Medical School, University of Surrey, Guildford, UK

    H S Pandha

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  1. S Hamdan
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Correspondence to G E Blair.

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Hamdan, S., Verbeke, C., Fox, N. et al. The roles of cell surface attachment molecules and coagulation Factor X in adenovirus 5-mediated gene transfer in pancreatic cancer cells. Cancer Gene Ther 18, 478–488 (2011). https://doi.org/10.1038/cgt.2011.17

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