Circulating fibroblast-like cells in men with metastatic prostate cancer

Authors

  • Michelle L. Jones,

    1. Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Javed Siddiqui,

    1. Department of Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan
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  • Kenneth J. Pienta,

    1. Department of Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan
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  • Robert H. Getzenberg

    Corresponding author
    1. Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Departments of Oncology, and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland
    • 600 N. Wolfe St., Marburg 121, Baltimore, MD 21287.
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  • This work was performed in the Departments of Urology and Pathology at the Johns Hopkins University School of Medicine and in the Department of Urology and the Comprehensive Cancer Center at the University of Michigan Medical School.

  • The authors have no conflicts of interest to disclose.

Abstract

BACKGROUND

Metastatic prostate cancer is an incurable disease. During the development of this disease, prostate cancer cells enter the bloodstream as single cells or clusters of cells. Prostate fibroblasts, a cancer-promoting cell type in the prostate cancer microenvironment, could in theory incorporate into these migrating cell clusters or follow cancer cells into the bloodstream through holes in the tumor vasculature. Based on this idea, we hypothesized that fibroblast-like cells, defined here as cytokeratin 8/18/19/DAPI+/CD45/vimentin+ cells, are present in the blood of men with metastatic prostate cancer.

METHODS

Veridex's CellSearch® system was used to immunomagnetically capture EpCAM+ cells and clusters of cells heterogeneous for EpCAM expression from the blood of men with metastatic prostate cancer, localized cancer, and no known cancer, and immunostain them for the presence of cytokeratins 8/18/19, a nucleus, CD45, and vimentin. Fibroblast-like cells were then quantified.

RESULTS

Fibroblast-like cells were present in 58.3% of men with metastatic prostate cancer but not in any men with localized prostate cancer or no known cancer. The presence of these cells correlated with certain known indicators of poor prognosis: ≥5 circulating tumor cells, defined here as cytokeratin 8/18/19+/DAPI+/CD45 cells, per 7.5 ml of blood, and a relatively high serum prostate-specific antigen level of ≥20 ng/ml.

CONCLUSIONS

The presence of fibroblast-like cells in the blood may provide prognostic information as well as information about the biology of metastatic prostate cancer. Prostate 73: 176–181, 2013. © 2012 Wiley Periodicals, Inc.

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