HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2007-0440v1 26/2/364    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cho, R. W. Articles by Clarke, M. F. Search for Related Content PubMed PubMed Citation Articles by Cho, R. W. Articles by Clarke, M. F.

CANCER STEM CELLS

Isolation and Molecular Characterization of Cancer Stem Cells in MMTV-Wnt-1 Murine Breast Tumors

Departments of ^aPediatrics,
^dStatistics, and
^eInternal Medicine and
^gProgram in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA;
^bOncomed Pharmaceuticals Inc., Redwood City, California, USA;
Departments of ^cRadiation Oncology and
^fGenetics, Stanford University, Palo Alto, California, USA;
^hStanford Institute for Stem Cell Biology and Regenerative Medicine, Palo Alto, California, USA

Key Words. Wnt-1 • Cancer stem cell • Breast cancer • Murine

Correspondence: Correspondence: Michael F. Clarke, M.D., Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, California, 94304, USA. Telephone: 650-725-2495; Fax: 650-736-2961; e-mail: mfclarke{at}stanford.edu

Received on June 6, 2007; accepted for publication on October 17, 2007.

First published online in STEM CELLS EXPRESS  November 1, 2007.


In human breast cancers, a phenotypically distinct minority population of tumorigenic (TG) cancer cells (sometimes referred to as cancer stem cells) drives tumor growth when transplanted into immunodeficient mice. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to the study of human breast cancer. To do so, we used breast tumors of the mouse mammary tumor virus (MMTV)-Wnt-1 mice. MMTV-Wnt-1 breast tumors were harvested, dissociated into single-cell suspensions, and sorted by flow cytometry on Thy1, CD24, and CD45. Sorted cells were then injected into recipient background FVB/NJ female syngeneic mice. In six of seven tumors examined, Thy1+CD24+ cancer cells, which constituted approximately 1%–4% of tumor cells, were highly enriched for cells capable of regenerating new tumors compared with cells of the tumor that did not fit this profile ("not-Thy1+CD24+"). Resultant tumors had a phenotypic diversity similar to that of the original tumor and behaved in a similar manner when passaged. Microarray analysis comparing Thy1+CD24+ tumor cells to not-Thy1+CD24+ cells identified a list of differentially expressed genes. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.

This article has been cited by other articles:

				M. F. Clarke Introduction to Epithelial Stem Cells Am. Assoc. Cancer Res. Educ. Book, April 18, 2009; 2009(1): 179 - 180. [Full Text] [PDF]

				M. Santisteban, J. M. Reiman, M. K. Asiedu, M. D. Behrens, A. Nassar, K. R. Kalli, P. Haluska, J. N. Ingle, L. C. Hartmann, M. H. Manjili, et al. Immune-Induced Epithelial to Mesenchymal Transition In vivo Generates Breast Cancer Stem Cells Cancer Res., April 1, 2009; 69(7): 2887 - 2895. [Abstract] [Full Text] [PDF]

				T. Deng, J. C. Liu, K. I. Pritchard, A. Eisen, and E. Zacksenhaus Preferential Killing of Breast Tumor Initiating Cells by N,N-Diethyl-2-[4-(Phenylmethyl)Phenoxy]Ethanamine/Tesmilifene Clin. Cancer Res., January 1, 2009; 15(1): 119 - 130. [Abstract] [Full Text] [PDF]

				M.-L. Asselin-Labat, F. Vaillant, M. Shackleton, T. Bouras, G.J. Lindeman, and J.E. Visvader Delineating the Epithelial Hierarchy in the Mouse Mammary Gland Cold Spring Harb Symp Quant Biol, November 19, 2008; (2008) sqb.2008.73.020v2. [Abstract] [PDF]

				J.M Adams, P.N. Kelly, A. Dakic, S. Carotta, S.L. Nutt, and A. Strasser Role of "Cancer Stem Cells" and Cell Survival in Tumor Development and Maintenance Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.004v1. [Abstract] [PDF]

				F. Vaillant, M.-L. Asselin-Labat, M. Shackleton, N. C. Forrest, G. J. Lindeman, and J. E. Visvader The Mammary Progenitor Marker CD61/{beta}3 Integrin Identifies Cancer Stem Cells in Mouse Models of Mammary Tumorigenesis Cancer Res., October 1, 2008; 68(19): 7711 - 7717. [Abstract] [Full Text] [PDF]

				M. Zhang, F. Behbod, R. L. Atkinson, M. D. Landis, F. Kittrell, D. Edwards, D. Medina, A. Tsimelzon, S. Hilsenbeck, J. E. Green, et al. Identification of Tumor-Initiating Cells in a p53-Null Mouse Model of Breast Cancer Cancer Res., June 15, 2008; 68(12): 4674 - 4682. [Abstract] [Full Text] [PDF]