Isolation and Identification of Cancer Stem-Like Cells in Esophageal Carcinoma Cell Lines

被引:115
作者
Huang, Dingzhi [1 ,2 ]
Gao, Quanli [1 ,3 ]
Guo, Liping [1 ]
Zhang, Chunpeng [1 ]
Jiang, Wei [1 ]
Li, Hongxia [1 ]
Wang, Jing [1 ]
Han, Xiaohong [1 ]
Shi, Yuankai [1 ]
Lu, Shih Hsin [1 ,3 ]
机构
[1] Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China
[2] Tianjin Canc Hosp, Dept Gastrointestinal Oncol, Tianjin, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Canc Res Ctr, Zhengzhou, Henan, Peoples R China
关键词
SUBPOPULATION; HIERARCHY; PATHWAY; ORIGIN;
D O I
10.1089/scd.2008.0033
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Side population (SP) cells may play an important role in tumorigenesis and cancer therapy. We isolate and identify the cancer stem-like cells in human esophageal carcinoma (EC) cell lines, EC9706 and EC109 cells labeled with Hoechst 33342. Both the cell lines contained SP cells, and the cells that had the strongest dye efflux activity ("Tip"-SP cell) in EC9706 had higher clone formation efficiency than non-SP cells. When transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, "Tip"-SP cells showed at least 50 times higher tumorigenicity than non-SP cells. Microarray analysis discriminated a differential gene expression profile between "Tip"-SP and non-SP cells, which is further tested using quantitative real-time RT-PCR. It is ascertained that several important stem cell-related genes (including OCT-4, SOX-2, BMI-1, and ZFX), two ATP-binding cassette (ABC) transporter genes (ABCG2 and ABCA5), and three Wnt and two Notch signal pathway-related genes (such as FZD10, PTGS2, KLF5, TTK, and RBM15) were upregulated in "Tip"-SP cells. Western blot showed a higher expression of beta-catenin protein in "Tip"-SP cells. All these indicated that the minority population described as "Tip"-SP cells possessed cancer stem cell character. Further understanding of tumor stem cell-specific traits will offer insights on the early stages of tumorigenesis for prevention and enhanced selectivity of antitumor therapeutics.
引用
收藏
页码:465 / 473
页数:9
相关论文
共 33 条
[11]  
HO MM, 2008, CANCER RES, V15, P4827
[12]   Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line [J].
Kondo, T ;
Setoguchi, T ;
Taga, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (03) :781-786
[13]   Identification of pancreatic cancer stem cells [J].
Li, Chenwei ;
Heidt, David G. ;
Dalerba, Piero ;
Burant, Charles F. ;
Zhang, Lanjing ;
Adsay, Volkan ;
Wicha, Max ;
Clarke, Michael F. ;
Simeone, Diane M. .
CANCER RESEARCH, 2007, 67 (03) :1030-1037
[14]   Targeted therapy for cancer stem cells: the patched pathway and ABC transporters [J].
Lou, H. ;
Dean, M. .
ONCOGENE, 2007, 26 (09) :1357-1360
[15]   Rbm15 modulates notch-induced transcriptional activation and affects myeloid differentiation [J].
Ma, Xianyong ;
Renda, Matthew J. ;
Wang, Lin ;
Cheng, Ee-chun ;
Niu, Chao ;
Morris, Stephan W. ;
Chi, Andrew S. ;
Krause, Diane S. .
MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (08) :3056-3064
[16]   Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells [J].
Matsuzaki, Y ;
Kinjo, K ;
Mulligan, RC ;
Okano, H .
IMMUNITY, 2004, 20 (01) :87-93
[17]   Therapeutic potential of antibodies against FZD10, a cell-surface protein, for synovial sarcomas [J].
Nagayama, S ;
Fukukawa, C ;
Katagiri, T ;
Okamoto, T ;
Aoyama, T ;
Oyaizu, N ;
Imamura, M ;
Toguchida, J ;
Nakamura, Y .
ONCOGENE, 2005, 24 (41) :6201-6212
[18]   A human colon cancer cell capable of initiating tumour growth in immunodeficient mice [J].
O'Brien, Catherine A. ;
Pollett, Aaron ;
Gallinger, Steven ;
Dick, John E. .
NATURE, 2007, 445 (7123) :106-110
[19]   Translational repression determines a neuronal potential in Drosophila asymmetric cell division [J].
Okabe, M ;
Imai, T ;
Kurusu, M ;
Hiromi, Y ;
Okano, H .
NATURE, 2001, 411 (6833) :94-98
[20]   ESTIMATES OF THE WORLDWIDE FREQUENCY OF 16 MAJOR CANCERS IN 1980 [J].
PARKIN, DM ;
LAARA, E ;
MUIR, CS .
INTERNATIONAL JOURNAL OF CANCER, 1988, 41 (02) :184-197