Nature Medicine
3, 402 - 408 (1997)
doi:10.1038/nm0497-402
Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID miceKaren A. Klein1*, Robert E. Reiter2*, James Redula1, Hamid Moradi1, Xaio Lin Zhu6, Arthur R. Brothman, Dolores J. Lamb8, Marco Marcelli7, Arie Belldegrun2, Owen N. Witte3, 4, 5
& Charles L. Sawyers1, 5, 9
1Departments of Medicine, University of California Los Angeles, 11-934 Factor Building, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1678, USA
2Departments of Urology, University of California Los Angeles, 11-934 Factor Building, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1678, USA
3Departments of Microbiology and Molecular Genetics, University of California Los Angeles, 11-934 Factor Building, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1678, USA
4Howard Hughes Medical Institute, University of California Los Angeles, 11-934 Factor Building, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1678, USA
5Molecular Biology Institute, University of California Los Angeles, 11-934 Factor Building, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1678, USA
6Departments of Pediatrics and Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
7Departments of Medicine and Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
8Urology and Cell Biology Baylor College of Medicine, Houston, Texas 77030, USA
*These authors contributed equally to this work.
9Correspondence should be addressed to C.L.S 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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