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

被引:331
作者
Klein, KA
Reiter, RE
Redula, J
Morad, H
Zhu, XL
Brothman, AR
Lamb, DJ
Marcelli, M
Belldegrun, A
Witte, ON
Sawyers, CL
机构
[1] UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90095
[2] UNIV CALIF LOS ANGELES,SCH MED,DEPT UROL,LOS ANGELES,CA 90095
[3] UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & MOL GENET,LOS ANGELES,CA 90095
[4] UNIV CALIF LOS ANGELES,SCH MED,HOWARD HUGHES MED INST,LOS ANGELES,CA 90095
[5] UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90095
[6] UNIV UTAH,SCH MED,DEPT PEDIAT,SALT LAKE CITY,UT 84132
[7] UNIV UTAH,SCH MED,DEPT HUMAN GENET,SALT LAKE CITY,UT 84132
[8] BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030
[9] BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030
[10] BAYLOR COLL MED,DEPT UROL,HOUSTON,TX 77030
[11] BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030
关键词
D O I
10.1038/nm0497-402
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:402 / 408
页数:7
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