Identification of cancer stem cell-like cells from human epithelial ovarian carcinoma cell line

被引:87
作者
Shi, M. F. [1 ]
Jiao, J. [1 ]
Lu, W. G. [1 ]
Ye, F. [1 ]
Ma, D. [3 ]
Dong, Q. G. [2 ]
Xie, X. [1 ]
机构
[1] Zhejiang Univ, Dept Gynecol Oncol, Womens Hosp, Sch Med,Womens Reprod Hlth Lab Zhejiang Prov, Hangzhou 310003, Zhejiang, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Shanghai 200030, Peoples R China
[3] Huazhong Univ Sci & Technol, Canc Biol Res Ctr, Tongji Hosp, Tongji Med Coll, Wuhan, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
Cancer stem cells; Ovarian carcinoma; CD44; CD24; MESENCHYMAL TRANSITION; C-KIT; STEM/PROGENITOR CELLS; INITIATING CELLS; EXPRESSION; PROGRESSION; TUMORS; POPULATION; DISEASE; MARKERS;
D O I
10.1007/s00018-010-0420-9
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
Cancer stem cells (CSCs) play an important role in the development, invasion, and drug resistance of carcinoma, but the exact phenotype and characteristics of ovarian CSCs are still disputable. In this study, we identified cancer stem cell-like cells (CSC-LCs) and investigated their characteristics from the ovarian adenocarcinoma cell line 3AO. Our results showed that CSC-LCs were enriched in sphere-forming test and highly expressed CD44(+)CD24(-). The spheres and CD24(-) cells possessed strong tumorigenic ability by transplantation into nonobese diabetic/severe combined immunodeficient mice. CD44(+)CD24(-) cells expressed stem cell markers and differentiated to CD44(+)CD24(+) cells by immunofluorescence assay and fluorescence-activated cell-sorting analysis. In vitro experiments verified that CD44(+)CD24(-) cells were markedly resistant to carboplatin and paclitaxol. In conclusion, our study identifies the CD44(+)CD24(-) phenotype, self-renewal, high tumorigenicity, differentiation potential, and drug resistance of ovarian CSC-LCs. Our findings may provide the evidence needed to explore a new strategy in the treatment of ovarian cancer.
引用
收藏
页码:3915 / 3925
页数:11
相关论文
共 42 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]   Epigenetic regulation of CD133 and tumorigenicity of CD133+ovarian cancer cells [J].
Baba, T. ;
Convery, P. A. ;
Matsumura, N. ;
Whitaker, R. S. ;
Kondoh, E. ;
Perry, T. ;
Huang, Z. ;
Bentley, R. C. ;
Mori, S. ;
Fujii, S. ;
Marks, J. R. ;
Berchuck, A. ;
Murphy, S. K. .
ONCOGENE, 2009, 28 (02) :209-218
[3]   Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer [J].
Bapat, SA ;
Mali, AM ;
Koppikar, CB ;
Kurrey, NK .
CANCER RESEARCH, 2005, 65 (08) :3025-3029
[4]   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
[5]   ABC transporters as phenotypic markers and functional regulators of stem cells [J].
Bunting, KD .
STEM CELLS, 2002, 20 (01) :11-20
[6]   Self-renewal of teratocarcinoma and embryonic stem cells [J].
Chambers, I ;
Smith, A .
ONCOGENE, 2004, 23 (43) :7150-7160
[7]  
Clarke Michael F, 2006, Cancer Res, V66, P9339, DOI 10.1158/0008-5472.CAN-06-3126
[8]   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
[9]   Cancer stem cells: implications for the progression and treatment of metastatic disease [J].
Croker, A. K. ;
Allan, A. L. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2008, 12 (02) :374-390
[10]   Cancer stem cells: Models and concepts [J].
Dalerba, Piero ;
Cho, Robert W. ;
Clarke, Michael F. .
ANNUAL REVIEW OF MEDICINE, 2007, 58 :267-284