CD44+CD24- prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis

被引:344
作者
Hurt, E. M. [1 ]
Kawasaki, B. T. [1 ]
Klarmann, G. J. [2 ]
Thomas, S. B. [2 ]
Farrar, W. L. [1 ]
机构
[1] NCI, NIH, Ctr Canc Res, Canc Stem Cell Sect,Canc Prevent Lab, Ft Detrick, MD 21702 USA
[2] SAIC Frederick Inc, NCI, NIH, Basic Res Program, Ft Detrick, MD 21702 USA
关键词
prostate cancer; tumour stem cells; genomics; CD44; CD24; IN-VITRO PROPAGATION; TUMOR STEM-CELLS; PROSPECTIVE IDENTIFICATION; STEM/PROGENITOR CELLS;
D O I
10.1038/sj.bjc.6604242
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recent evidence supports the hypothesis that cancer stem cells are responsible for tumour initiation and formation. Using flow cytometry, we isolated a population of CD44(+)CD24(-) prostate cells that display stem cell characteristics as well as gene expression patterns that predict overall survival in prostate cancer patients. CD44(+)CD24(-) cells form colonies in soft agar and form tumours in NOD/SCID mice when as few as 100 cells are injected. Furthermore, CD44(+)CD24(-) cells express genes known to be important in stem cell maintenance, such as BMI-1 and Oct-3/4. Moreover, we can maintain CD44(+)CD24(-) prostate stem-like cells as nonadherent spheres in serum-replacement media without substantially shifting gene expression. Addition of serum results in adherence to plastic and shifts gene expression patterns to resemble the differentiated parental cells. Thus, we propose that CD44(+)CD24(-) prostate cells are stem-like cells responsible for tumour initiation and we provide a genomic definition of these cells and the differentiated cells they give rise to. Furthermore, gene expression patterns of CD44(+)CD24(-) cells have a genomic signature that is predictive of poor patient prognosis. Therefore, CD44(+)CD24(-) LNCaP prostate cells offer an attractive model system to both explore the biology important to the maintenance and differentiation of prostate cancer stem cells as well as to develop the therapeutics, as the gene expression pattern in these cells is consistent with poor survival in prostate cancer patients.
引用
收藏
页码:756 / 765
页数:10
相关论文
共 26 条
[1]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[2]  
*AM CANC I, 2006, PROSTR CANC FACTS FI
[3]   Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].
Bonnet, D ;
Dick, JE .
NATURE MEDICINE, 1997, 3 (07) :730-737
[4]   ESTIMATION OF LIVER-TUMOR VOLUME USING DIFFERENT FORMULAS - AN EXPERIMENTAL-STUDY IN RATS [J].
CARLSSON, G ;
GULLBERG, B ;
HAFSTROM, L .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 1983, 105 (01) :20-23
[5]   Prospective identification of tumorigenic prostate cancer stem cells [J].
Collins, AT ;
Berry, PA ;
Hyde, C ;
Stower, MJ ;
Maitland, NJ .
CANCER RESEARCH, 2005, 65 (23) :10946-10951
[6]   Tumour stem cells and drug resistance [J].
Dean, M ;
Fojo, T ;
Bates, S .
NATURE REVIEWS CANCER, 2005, 5 (04) :275-284
[7]   In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells [J].
Dontu, G ;
Abdallah, WM ;
Foley, JM ;
Jackson, KW ;
Clarke, MF ;
Kawamura, MJ ;
Wicha, MS .
GENES & DEVELOPMENT, 2003, 17 (10) :1253-1270
[8]   A tumorigenic subpopulation with stem cell properties in melanomas [J].
Fang, D ;
Nguyen, TK ;
Leishear, K ;
Finko, R ;
Kulp, AN ;
Hotz, S ;
Van Belle, PA ;
Xu, XW ;
Elder, DE ;
Herlyn, M .
CANCER RESEARCH, 2005, 65 (20) :9328-9337
[9]  
*I LAB AN RES COLS, 1996, GUID CAR US LAB AN
[10]   Identification of bronchioalveolar stem cells in normal lung and lung cancer [J].
Kim, CFB ;
Jackson, EL ;
Woolfenden, AE ;
Lawrence, S ;
Babar, I ;
Vogel, S ;
Crowley, D ;
Bronson, RT ;
Jacks, T .
CELL, 2005, 121 (06) :823-835