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Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice

Nature Medicine volume 3, pages 402–408 (1997)Cite this article

Abstract

Prostate cancer mortality results from metastasis to bone and hormone-independent tumor growth. Models to study these progressive changes are lacking. Here we describe the propagation of advanced human prostate cancer by direct transfer of surgical samples from patients into immune-deficient male SCID mice. Explants from six of eight patients formed prostate tumors and two showed unique cytogenetic, biologic and molecular features that were retained through six or more passages. One grew in an androgen-independent fashion, whereas the second formed tumors that regressed following castration then regrew. Micrometastatic disease was detected in the hematopoietic tissues of half of the recipient mice. Thus selected specimens of advanced human prostate cancer can be propagated in SCID mice in a manner that recapitulates the clinical transition from androgen-sensitive to androgen-independent growth, accompanied by micrometastasis.

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Author notes

  1. Karen A. Klein and Robert E. Reiter: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Medicine, University of California Los Angeles, UCLA School of Medicine, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, California, 90095-1678, USA

    James Redula, Hamid Moradi & Charles L. Sawyers

  2. Departments of Urology, University of California Los Angeles, UCLA School of Medicine, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, California, 90095-1678, USA

    Arie Belldegrun

  3. Departments of Microbiology and Molecular Genetics, University of California Los Angeles, UCLA School of Medicine, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, California, 90095-1678, USA

    Owen N. Witte

  4. Howard Hughes Medical Institute, University of California Los Angeles, UCLA School of Medicine, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, California, 90095-1678, USA

    Owen N. Witte

  5. Molecular Biology Institute, University of California Los Angeles, UCLA School of Medicine, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, California, 90095-1678, USA

    Owen N. Witte & Charles L. Sawyers

  6. Departments of Pediatrics and Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, 84132, USA

    Xaio Lin Zhu

  7. Departments of Medicine and Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    Marco Marcelli

  8. Urology and Cell Biology Baylor College of Medicine, Houston, Texas, 77030, USA

    Dolores J. Lamb

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  1. Karen A. Klein
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Klein, K., Reiter, R., Redula, J. et al. Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice. Nat Med 3, 402–408 (1997). https://doi.org/10.1038/nm0497-402

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