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[Cancer Research 65, 6207-6219, July 15, 2005]
© 2005 American Association for Cancer Research

Cell and Tumor Biology

Side Population Is Enriched in Tumorigenic, Stem-Like Cancer Cells, whereas ABCG2+ and ABCG2– Cancer Cells Are Similarly Tumorigenic

Lubna Patrawala1, Tammy Calhoun1, Robin Schneider-Broussard1, Jianjun Zhou1, Kent Claypool1 and Dean G. Tang1,2

1 Department of Carcinogenesis, Science Park-Research Division, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas and 2 Program in Environmental and Molecular Carcinogenesis, Graduate School of Biomedical Sciences, Houston, Texas

Requests for reprints: Dean Tang, Department of Carcinogenesis, Science Park-Research Division, The University of Texas M.D. Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX 78957. Phone: 512-237-9575; Fax: 512-237-2475; E-mail: dtang{at}mdanderson.org.

Recently, several human cancers including leukemia and breast and brain tumors were found to contain stem-like cancer cells called cancer stem cells (CSC). Most of these CSCs were identified using markers that identify putative normal stem cells. In some cases, stem-like cancer cells were identified using the flow cytometry-based side population technique. In this study, we first show that ~30% of cultured human cancer cells and xenograft tumors examined (~30 in total) possess a detectable side population. Purified side population cells from two cell lines (U373 glioma and MCF7 breast cancer) and a xenograft prostate tumor (LAPC-9) are more tumorigenic than the corresponding non–side population cells. These side population cells also possess some intrinsic stem cell properties as they generate non–side population cells in vivo, can be further transplanted, and preferentially express some "stemness" genes, including Notch-1 and ß-catenin. Because the side population phenotype is mainly mediated by ABCG2, an ATP-binding cassette half-transporter associated with multidrug resistance, we subsequently studied ABCG2+ and ABCG2– cancer cells with respect to their tumorigenicity in vivo. Although side population cells show increased ABCG2 mRNA expression relative to the non–side population cells and all cancer cells and xenograft tumors examined express ABCG2 in a small fraction (0.5-3%) of the cells, highly purified ABCG2+ cancer cells, surprisingly, have very similar tumorigenicity to the ABCG2– cancer cells. Mechanistic studies indicate that ABCG2 expression is associated with proliferation and ABCG2+ cancer cells can generate ABCG2– cells. However, ABCG2– cancer cells can also generate ABCG2+ cells. Furthermore, the ABCG2– cancer cells form more and larger clones in the long-term clonal analyses and the ABCG2– population preferentially expresses several "stemness" genes. Taken together, our results suggest that (a) the side population is enriched with tumorigenic stem-like cancer cells, (b) ABCG2 expression identifies mainly fast-cycling tumor progenitors, and (c) the ABCG2– population contains primitive stem-like cancer cells.




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Home page
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B. Tang, N. Yoo, M. Vu, M. Mamura, J.-S. Nam, A. Ooshima, Z. Du, P.-Y. Desprez, M. R. Anver, A. M. Michalowska, et al.
Transforming Growth Factor-{beta} Can Suppress Tumorigenesis through Effects on the Putative Cancer Stem or Early Progenitor Cell and Committed Progeny in a Breast Cancer Xenograft Model
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[Abstract] [Full Text] [PDF]

Home page
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Side Population Cells Isolated from Mesenchymal Neoplasms Have Tumor Initiating Potential
Cancer Res., September 1, 2007; 67(17): 8216 - 8222.
[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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Stem Cells, May 1, 2007; 25(5): 1317 - 1325.
[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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Home page
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[Abstract] [Full Text] [PDF]

Home page
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Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 547 - 553.
[Abstract] [Full Text] [PDF]

Home page
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J. Biol. Chem., March 2, 2007; 282(9): 6854 - 6862.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. S. Chen, W. A. Woodward, F. Behbod, S. Peddibhotla, M. P. Alfaro, T. A. Buchholz, and J. M. Rosen
Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line
J. Cell Sci., February 1, 2007; 120(3): 468 - 477.
[Abstract] [Full Text] [PDF]

Home page
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W. A. Woodward, M. S. Chen, F. Behbod, M. P. Alfaro, T. A. Buchholz, and J. M. Rosen
WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells
PNAS, January 9, 2007; 104(2): 618 - 623.
[Abstract] [Full Text] [PDF]

Home page
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Characterization of stem cell-like cancer cells in immune-competent mice
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[Abstract] [Full Text] [PDF]

Home page
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Non-side-population hematopoietic stem cells in mouse bone marrow
Blood, October 15, 2006; 108(8): 2850 - 2856.
[Abstract] [Full Text] [PDF]

Home page
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X. Fan, W. Matsui, L. Khaki, D. Stearns, J. Chun, Y.-M. Li, and C. G. Eberhart
Notch Pathway Inhibition Depletes Stem-like Cells and Blocks Engraftment in Embryonal Brain Tumors.
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[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
F. Behbod, W. Xian, C. A. Shaw, S. G. Hilsenbeck, A. Tsimelzon, and J. M. Rosen
Transcriptional Profiling of Mammary Gland Side Population Cells
Stem Cells, April 1, 2006; 24(4): 1065 - 1074.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. P. Hill
Identifying Cancer Stem Cells in Solid Tumors: Case Not Proven
Cancer Res., February 15, 2006; 66(4): 1891 - 1896.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
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Notch Signaling
Clin. Cancer Res., February 15, 2006; 12(4): 1074 - 1079.
[Full Text] [PDF]


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