Human Epithelial Basal Cells Are Cells of Origin of Prostate Cancer, Independent of CD133 Status§

Authors

  • Renea A. Taylor,

    Corresponding author
    1. Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
    • Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
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    • Telephone: +61-3-9902-9287; Fax: +61-3-9902-9223

  • Roxanne Toivanen,

    1. Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
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  • Mark Frydenberg,

    1. Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
    2. Department of Surgery, Monash University, Clayton, Victoria, Australia
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  • John Pedersen,

    1. Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
    2. TissuPath Laboratories, Hawthorn, Victoria, Australia
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  • Laurence Harewood,

    1. Epworth Eastern Hospital, Victoria, Australia
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  • Australian Prostate Cancer Bioresource,

    1. Department of Surgery, University of Melbourne and Epworth Health Care Group, Victoria, Australia
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  • Anne T. Collins,

    1. Department of Biology, University of York, York, United Kingdom
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  • Norman J. Maitland,

    1. Department of Biology, University of York, York, United Kingdom
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  • Gail P. Risbridger

    1. Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
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  • Author contributions: R.A.T. and R.T.: conception and design, collection and assembly of data, and analysis and interpretation and manuscript writing; M.F., J.P., L.H., and A.P.C.B.: provision of patient tissues; A.T.C. and N.J.M.: conception and design and intellectual input; G.P.R.: conception and design, data interpretation and manuscript writing, and final approval of the manuscript. R.A.T. and R.T. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS March 30, 2012.

Abstract

Normal prostatic epithelium is composed of basal and luminal cells. Prostate cancer can be initiated in both benign basal and luminal stem cells, but because basal cell markers are not expressed in patient tumors, the former result was unexpected. Since the cells of origin of prostate cancer are important therapeutic targets, we sought to provide further proof that basal stem cells have tumorigenic potential. Prostatic basal cells were enriched based on α2β1integrinhi expression and further enriched for stem cells using CD133 in nontumorigenic BPH-1 cells. Human embryonic stem cells (hESCs) were also used as a source of normal stem cells. To test their tumorigenicity, we used two alternate stromal-based approaches; (a) recombination with human cancer-associated fibroblasts (CAFs) or (b) recombination with embryonic stroma (urogenital mesenchyme) and treated host mice with testosterone and 17β-estradiol. Enriched α2β1integrinhi basal cells from BPH-1 cells resulted in malignant tumor formation using both assays of tumorigenicity. Surprisingly, the tumorigenic potential did not reside in the CD133+ stem cells but was consistently observed in the CD133 population. CAFs also failed to induce prostatic tumors from hESCs. These data confirmed that benign human basal cells include cells of origin of prostate cancer and reinforced their importance as therapeutic targets. In addition, our data suggested that the more proliferative CD133 basal cells are more susceptible to tumorigenesis compared to the CD133+-enriched stem cells. These findings challenge the current dogma that normal stem cells and cells of origin of cancer are the same cell type(s). STEM CELLS2012;30:1087–1096

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