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Expression and function of the coxsackie and adenovirus receptor in Barrett's esophagus and associated neoplasia

Cancer Gene Therapy volume 16, pages 508–515 (2009)Cite this article

Abstract

Cell surface presence of the coxsackie and adenovirus receptor (CAR) is considered a crucial prerequisite for the uptake of attenuated adenovirus. In cancers, however, a frequent loss of CAR has been noted potentially hampering the success of adenovirus-based therapy. In esophageal Barrett's carcinomas and its precursor lesions CAR presence has not been systematically determined yet. Immunohistochemical assessment in tissue specimens of 111 patients revealed CAR-positivity in all cases of Barrett's esophagus, including various degrees of intraepithelial neoplasia. In contrast, no considerable CAR presence was seen in squamous esophageal epithelium. Among Barrett's carcinomas, 93% displayed CAR presence, whereas CAR-negativity was observed preferentially in advanced cancers. Aiming to evaluate whether this loss of CAR impacts tumor-biologic properties of esophageal adenocarcinomas we studied cell lines OE19 and OE33 and observed an increased proliferation, migration and invasion upon siRNA-mediated functional CAR knock down. In conclusion, our results indicate that CAR may provide a valuable target for adenovirus-based therapy of Barrett's carcinomas and its precursor lesions. These data do also suggest that CAR does not contribute substantially to carcinogenesis in Barrett's esophagus, however, it may be speculated that loss of CAR promotes tumor progression in advanced stages of Barrett's carcinomas.

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Abbreviations

BC:

Barrett's carcinoma

BE:

Barrett's esophagus

CAR:

coxsackie and adenovirus receptor

IN:

intraepithelial neoplasia

TJ:

tight junction

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Acknowledgements

We thank Dr J Bergelson (Division of Infectious Diseases, Children's Hospital of Philadelphia, PA) for providing the ‘CHO-CAR’ cell line.

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Authors and Affiliations

  1. Department of Interdisciplinary Endoscopy, University Hospital Hamburg Eppendorf, Hamburg, Germany

    M Anders & T Rösch

  2. Department of Internal Medicine, Divisions of Gastroenterology and Hepatology, Charité Medical School, Campus Virchow, Berlin, Germany

    K Küster & B Wiedenmann

  3. Institute of Pathology, Rosenheim, Germany

    I Becker

  4. Department of Pathology, Technical University of Munich, Munich, Germany

    H Höfler

  5. Department of Surgery, Paracelsus Medical University, Salzburg, Austria

    H J Stein

  6. Department of Internal Medicine II, Technical University of Munich, Munich, Germany

    A Meining

  7. Institute of Pathology, Munich, Germany

    M Sarbia

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  1. M Anders
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Correspondence to M Anders.

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Anders, M., Rösch, T., Küster, K. et al. Expression and function of the coxsackie and adenovirus receptor in Barrett's esophagus and associated neoplasia. Cancer Gene Ther 16, 508–515 (2009). https://doi.org/10.1038/cgt.2008.103

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  • DOI: https://doi.org/10.1038/cgt.2008.103

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