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Human urinary bladder carcinomas express adenovirus attachment and internalization receptors

Gene Therapy volume 9, pages 547–553 (2002)Cite this article

Abstract

The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins αvβ3 and/or αvβ5 are needed. Since there have been reports of loss of CVADR in bladder cancer cell lines, we wanted to investigate the expression of this receptor in bladder carcinoma biopsies. Surgical biopsies, as well as five human bladder cancer cell lines, were analyzed for expression of CVADR, the integrins αvβ3 and αvβ5 and MHC class I. Further, we studied the ability to transduce these cell lines using adenoviral vectors. Immunohistochemistry revealed that all biopsies (27/27) were positive for CVADR. Some variation in expression was evident, and superficially growing tumors stained more strongly than invasive ones. Most human tumors expressed the integrin αvβ5 (14/24), whereas integrin αvβ3 was less frequently seen (3/20). The established cell lines were efficiently transduced with adenoviral vectors, and transduction could be reduced with anti-CVADR antibodies. The abundance of appropriate viral receptors on tumor biopsy cells is a further argument for using adenoviral vectors in gene therapy of bladder cancer.

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Acknowledgements

This study was supported by The Swedish Cancer Society, The Swedish Gene Therapy Program and the Lions’ Cancer Fund at Uppsala University Hospital. The authors thank Dr Frank Graham, McMaster University for providing the Ad-dl70-3 vector, and Professor Jörgen Carlsson, Uppsala University and PhD Agneta Richter-Dahlfors, Karolinska Institute, for providing the cell lines, respectively.

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Authors and Affiliations

  1. Clinical Immunology Division, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden

    A Loskog, T Hedlund & T H Tötterman

  2. Experimental Urology Division, Rudbeck Laboratory, University Hospital, Uppsala, Sweden

    K Wester, M de la Torre & P-U Malmström

  3. Cell and Molecular Biology Division, Karolinska Institute, Stockholm, Sweden

    L Philipson

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  1. A Loskog
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  2. T Hedlund
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Loskog, A., Hedlund, T., Wester, K. et al. Human urinary bladder carcinomas express adenovirus attachment and internalization receptors. Gene Ther 9, 547–553 (2002). https://doi.org/10.1038/sj.gt.3301689

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