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Suppression of tumorigenicity by adenovirus-mediated gene transfer of decorin

Oncogene volume 21, pages 3688–3695 (2002)Cite this article

Abstract

There is mounting evidence that decorin inhibits the growth of various tumor cell lines when either over-expressed in vitro or provided as a recombinant protein. The mechanism of action is primarily via a protracted inactivation of the epidermal growth factor receptor (EGFR) tyrosine kinase. In this study we explored the possibility of retarding the growth of tumor xenografts by decorin gene delivery into the growing neoplastic tissues. We demonstrate that transient transgene expression of replication-deficient adenovirus-containing decorin causes a significant growth inhibition of colon and squamous carcinoma tumor xenografts. These cytostatic effects were achieved with relatively low viral titers and correlated with a reduced proliferative index and an attenuation of the EGFR phosphorylation in vivo. Thus, decorin gene therapy helps in retarding the growth of human tumors in immunocompromised animals and could represent a new independent or adjunctive therapeutic modality against cancer.

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Abbreviations

Ad-Dcn:

adenovirus-decorin

EGFR:

epidermal growth factor receptor

TGF-β:

transforming growth factor-β

pfu:

plaque-forming units

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Acknowledgements

We thank I Eichstetter for excellent technical assistance, C Munnery and C Buzas for help with the immunohistochemistry and immunofluorescence studies, respectively, L Fisher for providing valuable reagents, and M During for help with the real time PCR. This work was supported by grants from the National Institutes of Health, RO1 CA39481 and RO1 CA47282, and grants from the Department of the Army, DAMD17-00-1-0663 and DAMD17-00-1-0425 to RV Iozzo.

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Authors and Affiliations

  1. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania

    Charles C Reed & Renato V Iozzo

  2. PA 19107, USA

    Charles C Reed & Renato V Iozzo

  3. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

    Jack Gauldie

  4. Cellular Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, PA, USA

    Renato V Iozzo

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  1. Charles C Reed
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Correspondence to Renato V Iozzo.

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Reed, C., Gauldie, J. & Iozzo, R. Suppression of tumorigenicity by adenovirus-mediated gene transfer of decorin. Oncogene 21, 3688–3695 (2002). https://doi.org/10.1038/sj.onc.1205470

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