OriGene Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on January 7, 2004, 10.1073/pnas.0307618100
PNAS | January 20, 2004 | vol. 101 | no. 3 | 781-786


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (166)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kondo, T.
Right arrow Articles by Taga, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kondo, T.
Right arrow Articles by Taga, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

DEVELOPMENTAL BIOLOGY
Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line

Toru Kondo * {dagger} {ddagger} §, Takao Setoguchi {dagger} {ddagger} ¶, and Tetsuya Taga *

*Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan;{dagger}Centre for Brain Repair, University of Cambridge, E. D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, United Kingdom; and Department of Orthopaedic Surgery, Kagoshima Graduate School of Medicine and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan

Communicated by Martin C. Raff, University College London, London, United Kingdom, November 20, 2003 (received for review September 1, 2003)

Both stem cells and cancer cells are thought to be capable of unlimited proliferation. Paradoxically, however, some cancers seem to contain stem-like cells (cancer stem cells). To help resolve this paradox, we investigated whether established malignant cell lines, which have been maintained for years in culture, contain a subpopulation of stem cells. In this article, we show that many cancer cell lines contain a small side population (SP), which, in many normal tissues, is thought to contain the stem cells of the tissue. We demonstrate that in the absence of serum the combination of basic fibroblast growth factor and platelet-derived growth factor maintains SP cells in the C6 glioma cell line. Moreover, we show that C6 SP cells, but not non-SP cells, can generate both SP and non-SP cells in culture and are largely responsible for the in vivo malignancy of this cell line. Finally, we provide evidence that C6 SP cells can produce both neurons and glial cells in vitro and in vivo. We propose that many cancer cell lines contain a minor subpopulation of stem cells that is enriched in an SP, can be maintained indefinitely in culture, and is crucial for their malignancy.

Abbreviations: SP, side population; PDGF, platelet-derived growth factor; bFGF, basic fibroblast growth factor; NSC, neural stem cell; GFAP, glial fibrillary acidic protein; ABC, ATP-binding cassette; MDR, multidrug-resistant; BCRP1, breast cancer-resistant protein 1; MAP2, microtubule-associated protein 2.

{ddagger} T.K. and T.S. contributed equally to this work.

§ To whom correspondence should be sent at the {dagger}address. E-mail: tk294{at}cam.ac.uk.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 Clin. Cancer Res.Home page
X. Zhang, R. Komaki, L. Wang, B. Fang, and J. Y. Chang
Treatment of Radioresistant Stem-Like Esophageal Cancer Cells by an Apoptotic Gene-Armed, Telomerase-Specific Oncolytic Adenovirus
Clin. Cancer Res., May 1, 2008; 14(9): 2813 - 2823.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Engelmann, H. Shen, and O. J. Finn
MCF7 Side Population Cells with Characteristics of Cancer Stem/Progenitor Cells Express the Tumor Antigen MUC1
Cancer Res., April 1, 2008; 68(7): 2419 - 2426.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Li, X. Chen, T. Calhoun-Davis, K. Claypool, and D. G. Tang
PC3 Human Prostate Carcinoma Cell Holoclones Contain Self-renewing Tumor-Initiating Cells
Cancer Res., March 15, 2008; 68(6): 1820 - 1825.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. G. Gilg, S. L. Tye, L. B. Tolliver, W. G. Wheeler, R. P. Visconti, J. D. Duncan, F. V. Kostova, L. N. Bolds, B. P. Toole, and B. L. Maria
Targeting Hyaluronan Interactions in Malignant Gliomas and Their Drug-Resistant Multipotent Progenitors
Clin. Cancer Res., March 15, 2008; 14(6): 1804 - 1813.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
D. Thomas, S. Friedman, and R.-Y. Lin
Thyroid stem cells: lessons from normal development and thyroid cancer
Endocr. Relat. Cancer, March 1, 2008; 15(1): 51 - 58.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
U. D. Lichtenauer, I. Shapiro, K. Geiger, M. Quinkler, M. Fassnacht, R. Nitschke, K.-D. Ruckauer, and F. Beuschlein
Side Population Does Not Define Stem Cell-Like Cancer Cells in the Adrenocortical Carcinoma Cell Line NCI h295R
Endocrinology, March 1, 2008; 149(3): 1314 - 1322.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
K. Ieta, F. Tanaka, N. Haraguchi, Y. Kita, H. Sakashita, K. Mimori, T. Matsumoto, H. Inoue, H. Kuwano, and M. Mori
Biological and Genetic Characteristics of Tumor-Initiating Cells in Colon Cancer
Ann. Surg. Oncol., February 1, 2008; 15(2): 638 - 648.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Yin, P. Castagnino, and R. K. Assoian
ABCG2 Expression and Side Population Abundance Regulated by a Transforming Growth Factor {beta}-Directed Epithelial-Mesenchymal Transition
Cancer Res., February 1, 2008; 68(3): 800 - 807.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. Tang, B. T. Ang, and S. Pervaiz
Cancer stem cell: target for anti-cancer therapy
FASEB J, December 1, 2007; 21(14): 3777 - 3785.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Zhou, J. Wulfkuhle, H. Zhang, P. Gu, Y. Yang, J. Deng, J. B. Margolick, L. A. Liotta, E. Petricoin III, and Y. Zhang
Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance
PNAS, October 9, 2007; 104(41): 16158 - 16163.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
E. E. Bar, A. Chaudhry, A. Lin, X. Fan, K. Schreck, W. Matsui, S. Piccirillo, A. L. Vescovi, F. DiMeco, A. Olivi, et al.
Cyclopamine-Mediated Hedgehog Pathway Inhibition Depletes Stem-Like Cancer Cells in Glioblastoma
Stem Cells, October 1, 2007; 25(10): 2524 - 2533.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Wu, Q. Wei, V. Utomo, P. Nadesan, H. Whetstone, R. Kandel, J. S. Wunder, and B. A. Alman
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
 Stem CellsHome page
A. J. Ghods, D. Irvin, G. Liu, X. Yuan, I. R. Abdulkadir, P. Tunici, B. Konda, S. Wachsmann-Hogiu, K. L. Black, and J. S. Yu
Spheres Isolated from 9L Gliosarcoma Rat Cell Line Possess Chemoresistant and Aggressive Cancer Stem-Like Cells
Stem Cells, July 1, 2007; 25(7): 1645 - 1653.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. M. Ho, A. V. Ng, S. Lam, and J. Y. Hung
Side Population in Human Lung Cancer Cell Lines and Tumors Is Enriched with Stem-like Cancer Cells
Cancer Res., May 15, 2007; 67(10): 4827 - 4833.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Beier, P. Hau, M. Proescholdt, A. Lohmeier, J. Wischhusen, P. J. Oefner, L. Aigner, A. Brawanski, U. Bogdahn, and C. P. Beier
CD133+ and CD133- Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles
Cancer Res., May 1, 2007; 67(9): 4010 - 4015.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
K. Kato, M. Yoshimoto, K. Kato, S. Adachi, A. Yamayoshi, T. Arima, K. Asanoma, S. Kyo, T. Nakahata, and N. Wake
Characterization of side-population cells in human normal endometrium
Hum. Reprod., May 1, 2007; 22(5): 1214 - 1223.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Y. Zen, T. Fujii, S. Yoshikawa, H. Takamura, T. Tani, T. Ohta, and Y. Nakanuma
Histological and Culture Studies with Respect to ABCG2 Expression Support the Existence of a Cancer Cell Hierarchy in Human Hepatocellular Carcinoma
Am. J. Pathol., May 1, 2007; 170(5): 1750 - 1762.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
P. P. Szotek, H. L. Chang, L. Zhang, F. Preffer, D. Dombkowski, P. K. Donahoe, and J. Teixeira
Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation
Stem Cells, May 1, 2007; 25(5): 1317 - 1325.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Folkins, S. Man, P. Xu, Y. Shaked, D. J. Hicklin, and R. S. Kerbel
Anticancer Therapies Combining Antiangiogenic and Tumor Cell Cytotoxic Effects Reduce the Tumor Stem-Like Cell Fraction in Glioma Xenograft Tumors
Cancer Res., April 15, 2007; 67(8): 3560 - 3564.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Zheng, G. Shen, X. Yang, and W. Liu
Most C6 Cells Are Cancer Stem Cells: Evidence from Clonal and Population Analyses
Cancer Res., April 15, 2007; 67(8): 3691 - 3697.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Wang, L.-P. Guo, L.-Z. Chen, Y.-X. Zeng, and S. H. Lu
Identification of Cancer Stem Cell-Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line
Cancer Res., April 15, 2007; 67(8): 3716 - 3724.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Mitsutake, A. Iwao, K. Nagai, H. Namba, A. Ohtsuru, V. Saenko, and S. Yamashita
Characterization of Side Population in Thyroid Cancer Cell Lines: Cancer Stem-Like Cells Are Enriched Partly But Not Exclusively
Endocrinology, April 1, 2007; 148(4): 1797 - 1803.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Giangreco, K. R. Groot, and S. M. Janes
Lung Cancer and Lung Stem Cells: Strange Bedfellows?
Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 547 - 553.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Aguado, A. Carracedo, B. Julien, G. Velasco, G. Milman, R. Mechoulam, L. Alvarez, M. Guzman, and I. Galve-Roperh
Cannabinoids Induce Glioma Stem-like Cell Differentiation and Inhibit Gliomagenesis
J. Biol. Chem., March 2, 2007; 282(9): 6854 - 6862.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
X. Zheng, A. Seshire, B. Ruster, G. Bug, T. Beissert, E. Puccetti, D. Hoelzer, R. Henschler, and M. Ruthardt
Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RAR{alpha}-positive leukemic stem cells
Haematologica, March 1, 2007; 92(3): 323 - 331.
[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
 Proc. Natl. Acad. Sci. USAHome page
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
 Stem CellsHome page
K. Chaichana, G. Zamora-Berridi, J. Camara-Quintana, and A. Quinones-Hinojosa
Neurosphere Assays: Growth Factors and Hormone Differences in Tumor and Nontumor Studies
Stem Cells, December 1, 2006; 24(12): 2851 - 2857.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. A. Kruger, C. D. Kaplan, Y. Luo, H. Zhou, D. Markowitz, R. Xiang, and R. A. Reisfeld
Characterization of stem cell-like cancer cells in immune-competent mice
Blood, December 1, 2006; 108(12): 3906 - 3912.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Pellegatta, P. L. Poliani, D. Corno, F. Menghi, F. Ghielmetti, B. Suarez-Merino, V. Caldera, S. Nava, M. Ravanini, F. Facchetti, et al.
Neurospheres Enriched in Cancer Stem-Like Cells Are Highly Effective in Eliciting a Dendritic Cell-Mediated Immune Response against Malignant Gliomas
Cancer Res., November 1, 2006; 66(21): 10247 - 10252.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Balenci, I. D. Clarke, P. B. Dirks, N. Assard, F. Ducray, A. Jouvet, M.-F. Belin, J. Honnorat, and J. Baudier
IQGAP1 Protein Specifies Amplifying Cancer Cells in Glioblastoma Multiforme.
Cancer Res., September 15, 2006; 66(18): 9074 - 9082.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N. Auger, J. Thillet, K. Wanherdrick, A. Idbaih, M.-E. Legrier, B. Dutrillaux, M. Sanson, and M.-F. Poupon
Genetic alterations associated with acquired temozolomide resistance in SNB-19, a human glioma cell line.
Mol. Cancer Ther., September 1, 2006; 5(9): 2182 - 2192.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
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.
Cancer Res., August 1, 2006; 66(15): 7445 - 7452.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. P. Szotek, R. Pieretti-Vanmarcke, P. T. Masiakos, D. M. Dinulescu, D. Connolly, R. Foster, D. Dombkowski, F. Preffer, D. T. MacLaughlin, and P. K. Donahoe
Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness
PNAS, July 25, 2006; 103(30): 11154 - 11159.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Interv.Home page
M. Dean
CANCER STEM CELLS: Redefining the Paradigm of Cancer Treatment Strategies
Mol. Interv., June 1, 2006; 6(3): 140 - 148.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
N. Haraguchi, T. Utsunomiya, H. Inoue, F. Tanaka, K. Mimori, G. F. Barnard, and M. Mori
Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System
Stem Cells, March 1, 2006; 24(3): 506 - 513.
[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
 Physiol. GenomicsHome page
C. Decraene, R. Benchaouir, M.-A. Dillies, D. Israeli, S. Bortoli, C. Rochon, P. Rameau, A. Pitaval, D. T.-L. Roux, O. Danos, et al.
Global transcriptional characterization of SP and MP cells from the myogenic C2C12 cell line: effect of FGF6
Physiol Genomics, October 17, 2005; 23(2): 132 - 149.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Fang, T. K. Nguyen, K. Leishear, R. Finko, A. N. Kulp, S. Hotz, P. A. Van Belle, X. Xu, D. E. Elder, and M. Herlyn
A Tumorigenic Subpopulation with Stem Cell Properties in Melanomas
Cancer Res., October 15, 2005; 65(20): 9328 - 9337.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Locke, M. Heywood, S. Fawell, and I. C. Mackenzie
Retention of Intrinsic Stem Cell Hierarchies in Carcinoma-Derived Cell Lines
Cancer Res., October 1, 2005; 65(19): 8944 - 8950.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
E. M. Langenfeld, J. Bojnowski, J. Perone, and J. Langenfeld
Expression of Bone Morphogenetic Proteins in Human Lung Carcinomas
Ann. Thorac. Surg., September 1, 2005; 80(3): 1028 - 1032.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
J. W. Jonker, J. Freeman, E. Bolscher, S. Musters, A. J. Alvi, I. Titley, A. H. Schinkel, and T. C. Dale
Contribution of the ABC Transporters Bcrp1 and Mdr1a/1b to the Side Population Phenotype in Mammary Gland and Bone Marrow of Mice
Stem Cells, September 1, 2005; 23(8): 1059 - 1065.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Patrawala, T. Calhoun, R. Schneider-Broussard, J. Zhou, K. Claypool, and D. G. Tang
Side Population Is Enriched in Tumorigenic, Stem-Like Cancer Cells, whereas ABCG2+ and ABCG2- Cancer Cells Are Similarly Tumorigenic
Cancer Res., July 15, 2005; 65(14): 6207 - 6219.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Ponti, A. Costa, N. Zaffaroni, G. Pratesi, G. Petrangolini, D. Coradini, S. Pilotti, M. A. Pierotti, and M. G. Daidone
Isolation and In vitro Propagation of Tumorigenic Breast Cancer Cells with Stem/Progenitor Cell Properties
Cancer Res., July 1, 2005; 65(13): 5506 - 5511.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
F. Behbod and J. M. Rosen
Will cancer stem cells provide new therapeutic targets?
Carcinogenesis, April 1, 2005; 26(4): 703 - 711.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M.-H. Tai, C.-C. Chang, L.K. Olson, and J. E. Trosko
Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis
Carcinogenesis, February 1, 2005; 26(2): 495 - 502.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
T. Kondo and M. Raff
Chromatin remodeling and histone modification in the conversion of oligodendrocyte precursors to neural stem cells
Genes & Dev., December 1, 2004; 18(23): 2963 - 2972.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Lotem, H. Benjamin, D. Netanely, E. Domany, and L. Sachs
Induction in myeloid leukemic cells of genes that are expressed in different normal tissues
PNAS, November 9, 2004; 101(45): 16022 - 16027.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Galli, E. Binda, U. Orfanelli, B. Cipelletti, A. Gritti, S. De Vitis, R. Fiocco, C. Foroni, F. Dimeco, and A. Vescovi
Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma
Cancer Res., October 1, 2004; 64(19): 7011 - 7021.
[Abstract] [Full Text] [PDF]