Cancer Research Cancer Health Disparities Conference 2009 SU2C
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
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
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wicha, M. S.
Right arrow Articles by Dontu, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wicha, M. S.
Right arrow Articles by Dontu, G.
Related Collections
Right arrow Cellular Pathobiology
Right arrow Cellular Pathobiology: Proliferation, Senescence, and Death
Right arrow Point-Counterpoint
[Cancer Research 66, 1883-1890, February 15, 2006]
© 2006 American Association for Cancer Research

Reviews

Cancer Stem Cells: An Old Idea—A Paradigm Shift

Max S. Wicha, Suling Liu and Gabriela Dontu

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan

Requests for reprints: Max S. Wicha, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive, 6303 CCGC, Ann Arbor, MI 48109-0942. Phone: 734-936-1831; Fax: 734-615-3947; E-mail: mwicha{at}umich.edu.

Although the concept that cancers arise from "stem cells" or "germ cells" was first proposed about 150 years ago, it is only recently that advances in stem cell biology have given new impetus to the "cancer stem cell hypothesis." Two important related concepts of this hypothesis are that (a) tumors originate in either tissue stem cells or their immediate progeny through dysregulation of the normally tightly regulated process of self-renewal. As a result of this, (b) tumors contain a cellular subcomponent that retains key stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation albeit aberrant that contributes to cellular heterogeneity. Recent experimental evidence in a variety of tumors has lent strong support to the cancer stem cell hypothesis that represents a paradigm shift in our understanding of carcinogenesis and tumor cell biology. This hypothesis has fundamental implications for cancer risk assessment, early detection, prognostication, and prevention. Furthermore, the current development of cancer therapeutics based on tumor regression may have produced agents that kill differentiated tumor cells while sparing the rare cancer stem cell population. The development of more effective cancer therapies may thus require targeting this important cell population. (Cancer Res 2006; 66(4): 1883-90)

 



This article has been cited by other articles:


Home page
 Cancer Res.Home page
D. J. Vander Griend, W. L. Karthaus, S. Dalrymple, A. Meeker, A. M. DeMarzo, and J. T. Isaacs
The Role of CD133 in Normal Human Prostate Stem Cells and Malignant Cancer-Initiating Cells
Cancer Res., December 1, 2008; 68(23): 9703 - 9711.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
R.U. Lukacs, D.A. Lawson, L. Xin, Y. Zong, I. Garraway, A.S. Goldstein, S. Memarzadeh, and O.N. Witte
Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression
Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.012v1.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
M. P. Waalkes, J. Liu, D. R. Germolec, C. S. Trempus, R. E. Cannon, E. J. Tokar, R. W. Tennant, J. M. Ward, and B. A. Diwan
Arsenic Exposure In utero Exacerbates Skin Cancer Response in Adulthood with Contemporaneous Distortion of Tumor Stem Cell Dynamics
Cancer Res., October 15, 2008; 68(20): 8278 - 8285.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
I. A. Savtchouk, F. J. Mattie, and A. A. Ollis
Ceramide: From Embryos to Tumors
Sci. Signal., September 2, 2008; 1(35): jc1 - jc1.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Alix-Panabieres, S. Riethdorf, and K. Pantel
Circulating Tumor Cells and Bone Marrow Micrometastasis
Clin. Cancer Res., August 15, 2008; 14(16): 5013 - 5021.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
L. Melchor and J. Benitez
An integrative hypothesis about the origin and development of sporadic and familial breast cancer subtypes
Carcinogenesis, August 1, 2008; 29(8): 1475 - 1482.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Y. Xiao, Y. Ye, K. Yearsley, S. Jones, and S. H. Barsky
The Lymphovascular Embolus of Inflammatory Breast Cancer Expresses a Stem Cell-Like Phenotype
Am. J. Pathol., August 1, 2008; 173(2): 561 - 574.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
B. Das, R. Tsuchida, D. Malkin, G. Koren, S. Baruchel, and H. Yeger
Hypoxia Enhances Tumor Stemness by Increasing the Invasive and Tumorigenic Side Population Fraction
Stem Cells, July 1, 2008; 26(7): 1818 - 1830.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
B. M. Boman and M. S. Wicha
Cancer Stem Cells: A Step Toward the Cure
J. Clin. Oncol., June 10, 2008; 26(17): 2795 - 2799.
[Full Text] [PDF]

Home page
 JCOHome page
S. Sell and H. L. Leffert
Liver Cancer Stem Cells
J. Clin. Oncol., June 10, 2008; 26(17): 2800 - 2805.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. E. Eyler and J. N. Rich
Survival of the Fittest: Cancer Stem Cells in Therapeutic Resistance and Angiogenesis
J. Clin. Oncol., June 10, 2008; 26(17): 2839 - 2845.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
G. V. Glinsky
"Stemness" Genomics Law Governs Clinical Behavior of Human Cancer: Implications for Decision Making in Disease Management
J. Clin. Oncol., June 10, 2008; 26(17): 2846 - 2853.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. E.P. Prince and L. E. Ailles
Cancer Stem Cells in Head and Neck Squamous Cell Cancer
J. Clin. Oncol., June 10, 2008; 26(17): 2871 - 2875.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. D. Peacock and D. N. Watkins
Cancer Stem Cells and the Ontogeny of Lung Cancer
J. Clin. Oncol., June 10, 2008; 26(17): 2883 - 2889.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Zhang, C. Balch, M. W. Chan, H.-C. Lai, D. Matei, J. M. Schilder, P. S. Yan, T. H-M. Huang, and K. P. Nephew
Identification and Characterization of Ovarian Cancer-Initiating Cells from Primary Human Tumors
Cancer Res., June 1, 2008; 68(11): 4311 - 4320.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. A. Loeb, J. H. Bielas, R. A. Beckman, and I. W. Bodmer
Cancers Exhibit a Mutator Phenotype: Clinical Implications
Cancer Res., May 15, 2008; 68(10): 3551 - 3557.
[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
 CarcinogenesisHome page
G. W. Neill, W. J. Harrison, M. S. Ikram, T. D.L. Williams, L. S. Bianchi, S. K. Nadendla, J. L. Green, L. Ghali, A.-M. Frischauf, E. A. O'Toole, et al.
GLI1 repression of ERK activity correlates with colony formation and impaired migration in human epidermal keratinocytes
Carcinogenesis, April 1, 2008; 29(4): 738 - 746.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
D. M. Kristensen, J. E. Nielsen, N. E. Skakkebaek, N. Graem, G. K. Jacobsen, E. R.-D. Meyts, and H. Leffers
Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms
Hum. Reprod., April 1, 2008; 23(4): 775 - 782.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Potapova, A. M. Hoffman, A. K. Godwin, T. Al-Saleem, and P. Cairns
Promoter Hypermethylation of the PALB2 Susceptibility Gene in Inherited and Sporadic Breast and Ovarian Cancer
Cancer Res., February 15, 2008; 68(4): 998 - 1002.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Liu, C. Ginestier, E. Charafe-Jauffret, H. Foco, C. G. Kleer, S. D. Merajver, G. Dontu, and M. S. Wicha
BRCA1 regulates human mammary stem/progenitor cell fate
PNAS, February 5, 2008; 105(5): 1680 - 1685.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Kenyon and S. L. Gerson
The role of DNA damage repair in aging of adult stem cells
Nucleic Acids Res., December 26, 2007; (2007) gkm1064v1.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Adelaide, P. Finetti, I. Bekhouche, L. Repellini, J. Geneix, F. Sircoulomb, E. Charafe-Jauffret, N. Cervera, J. Desplans, D. Parzy, et al.
Integrated Profiling of Basal and Luminal Breast Cancers
Cancer Res., December 15, 2007; 67(24): 11565 - 11575.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. D. Minna, L. Girard, and Y. Xie
Tumor mRNA Expression Profiles Predict Responses to Chemotherapy
J. Clin. Oncol., October 1, 2007; 25(28): 4329 - 4336.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
J. N. Rich
Cancer Stem Cells in Radiation Resistance
Cancer Res., October 1, 2007; 67(19): 8980 - 8984.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
M. Mimeault and S. K. Batra
Interplay of distinct growth factors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies
Ann. Onc., October 1, 2007; 18(10): 1605 - 1619.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
V. K. Rajasekhar and M. Begemann
Concise Review: Roles of Polycomb Group Proteins in Development and Disease: A Stem Cell Perspective
Stem Cells, October 1, 2007; 25(10): 2498 - 2510.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
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
Cancer Res., September 15, 2007; 67(18): 8643 - 8652.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. J. Pietras and D. C. Marquez-Garban
Membrane-Associated Estrogen Receptor Signaling Pathways in Human Cancers
Clin. Cancer Res., August 15, 2007; 13(16): 4672 - 4676.
[Full Text] [PDF]

Home page
 Sci SignalHome page
I. A. Savtchouk, F. J. Mattie, and A. A. Ollis
Ceramide: from Embryos to Tumors
Sci. Signal., July 10, 2007; 2007(394): jc1 - jc1.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. E. Paulson, K. Rieger-Christ, M. A. McDevitt, C. Kuperwasser, J. Kim, V. E. Unanue, X. Zhang, M. Hu, R. Ruthazer, S. P. Berasi, et al.
Alterations of the HBP1 Transcriptional Repressor Are Associated with Invasive Breast Cancer
Cancer Res., July 1, 2007; 67(13): 6136 - 6145.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
R. R. Langley and I. J. Fidler
Tumor Cell-Organ Microenvironment Interactions in the Pathogenesis of Cancer Metastasis
Endocr. Rev., May 1, 2007; 28(3): 297 - 321.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
K. Polyak
Epigenetic Regulation of Stem Cell Phenotype and Differentiation
Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 111 - 114.
[Full Text] [PDF]

Home page
 aacredbookHome page
M. Fukunaga-Kalabis, L. Li, and M. Herlyn
Three-Dimensional Culture of Human Skin
Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 203 - 206.
[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. Pathol.Home page
H. Cui, B. Hu, T. Li, J. Ma, G. Alam, W. T. Gunning, and H.-F. Ding
Bmi-1 Is Essential for the Tumorigenicity of Neuroblastoma Cells
Am. J. Pathol., April 1, 2007; 170(4): 1370 - 1378.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. Mimeault, S. L. Johansson, G. Vankatraman, E. Moore, J.-P. Henichart, P. Depreux, M.-F. Lin, and S. K. Batra
Combined targeting of epidermal growth factor receptor and hedgehog signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer cells
Mol. Cancer Ther., March 1, 2007; 6(3): 967 - 978.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
P. Sansone, G. Storci, C. Giovannini, S. Pandolfi, S. Pianetti, M. Taffurelli, D. Santini, C. Ceccarelli, P. Chieco, and M. Bonafe
p66Shc/Notch-3 Interplay Controls Self-Renewal and Hypoxia Survival in Human Stem/Progenitor Cells of the Mammary Gland Expanded In Vitro as Mammospheres
Stem Cells, March 1, 2007; 25(3): 807 - 815.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. Houldsworth, J. E. Korkola, G. J. Bosl, and R. S. K. Chaganti
Biology and Genetics of Adult Male Germ Cell Tumors
J. Clin. Oncol., December 10, 2006; 24(35): 5512 - 5518.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
M. Lacroix
Significance, detection and markers of disseminated breast cancer cells
Endocr. Relat. Cancer, December 1, 2006; 13(4): 1033 - 1067.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Cui, J. Ma, J. Ding, T. Li, G. Alam, and H.-F. Ding
Bmi-1 Regulates the Differentiation and Clonogenic Self-renewal of I-type Neuroblastoma Cells in a Concentration-dependent Manner
J. Biol. Chem., November 10, 2006; 281(45): 34696 - 34704.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. S. Wicha
Cancer stem cells and metastasis: lethal seeds.
Clin. Cancer Res., October 1, 2006; 12(19): 5606 - 5607.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Axelrod, D. E. Axelrod, and K. J. Pienta
From the Cover: Evolution of cooperation among tumor cells
PNAS, September 5, 2006; 103(36): 13474 - 13479.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I. V. Litvinov, D. J. Vander Griend, Y. Xu, L. Antony, S. L. Dalrymple, and J. T. Isaacs
Low-Calcium Serum-Free Defined Medium Selects for Growth of Normal Prostatic Epithelial Stem Cells.
Cancer Res., September 1, 2006; 66(17): 8598 - 8607.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
W.-H. Zimmermann, M. Didie, S. Doker, I. Melnychenko, H. Naito, C. Rogge, M. Tiburcy, and T. Eschenhagen
Heart muscle engineering: An update on cardiac muscle replacement therapy
Cardiovasc Res, August 1, 2006; 71(3): 419 - 429.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Riggi, L. Cironi, P. Provero, M.-L. Suva, J.-C. Stehle, K. Baumer, L. Guillou, and I. Stamenkovic
Expression of the FUS-CHOP Fusion Protein in Primary Mesenchymal Progenitor Cells Gives Rise to a Model of Myxoid Liposarcoma.
Cancer Res., July 15, 2006; 66(14): 7016 - 7023.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Liu, G. Dontu, I. D. Mantle, S. Patel, N.-s. Ahn, K. W. Jackson, P. Suri, and M. S. Wicha
Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells.
Cancer Res., June 15, 2006; 66(12): 6063 - 6071.
[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 HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2006 by the American Association for Cancer Research.