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Decorin prevents metastatic spreading of breast cancer

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Abstract

Metastases in breast cancer are a vital concern in treatment, with epidermal growth factor receptor and ErbB2 strongly implicated in mediating tumor invasion and spreading. In this study, we investigated the role of decorin in suppressing both primary breast carcinomas and pulmonary metastases. We show that decorin causes marked growth suppression both in vitro and in vivo using a metastatic breast cancer cell line and an orthotopic mammary carcinoma model. Treatment with decorin protein core reduced primary tumor growth by 70% and eliminated observed metastases. An adenoviral vector containing the decorin transgene caused primary tumor retardation of 70%, in addition to greatly reducing observed metastases. Moreover, we demonstrate that ErbB2 phosphorylation and total receptor protein levels are reduced in this model system upon de novo expression of decorin under the control of a doxycycline-inducible promoter. Primary tumor growth in vivo was reduced by up to 67% upon decorin induction, and pulmonary metastases were markedly hampered as well. These effects are likely occurring through decorin's long-term downregulation of the ErbB2 tyrosine kinase cascade. These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases in this breast cancer model and could eventually lead to improved therapeutics for metastatic breast cancer.

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Abbreviations

Ad-Dcn:

adenovirus-decorin

EGFR:

epidermal growth factor receptor

PFU:

plaque-forming units

HRP:

horseradish peroxidase

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Acknowledgements

We thank JE Segall for providing the MTLn3 cells, and J Gauldie for the Ad-Decorin vector. This work was supported by grants from the National Institutes of Health RO1 CA39481 and RO1 CA47282, and a grant from the Department of the Army 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, PA, 19107, USA

    Charles C Reed, Anna Waterhouse, Siobhan Kirby, Paul Kay & Renato V Iozzo

  2. LifeCell Corporation, Branchburg, NJ, 08876, USA

    Rick T Owens & David J McQuillan

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

    Renato V Iozzo

Authors
  1. Charles C Reed
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  2. Anna Waterhouse
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  3. Siobhan Kirby
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  4. Paul Kay
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  5. Rick T Owens
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  6. David J McQuillan
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  7. Renato V Iozzo
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Correspondence to Renato V Iozzo.

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Reed, C., Waterhouse, A., Kirby, S. et al. Decorin prevents metastatic spreading of breast cancer. Oncogene 24, 1104–1110 (2005). https://doi.org/10.1038/sj.onc.1208329

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