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BMC Cancer
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Review

Breast cancer stem cells: tools and models to rely on

Authors: Emmanuelle Charafe-Jauffret, Christophe Ginestier, Daniel Birnbaum

Published in: BMC Cancer | Issue 1/2009

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Abstract

There is increasing evidence for the "cancer stem cell (CSC) hypothesis", which holds that cancers are driven by a cellular component that has stem cell properties, including self-renewal, tumorigenicity and multi-lineage differentiation capacity. Researchers and oncologists see in this model an explanation as to why cancer may be so difficult to cure, as well as a promising ground for novel therapeutic strategies. Given the specific stem cell features of self-renewal and differentiation, which drive tumorigenesis and contribute to cellular heterogeneity, each marker and assay designed to isolate and characterize CSCs has to be functionally validated. In this review, we survey tools and markers available or promising to identify breast CSCs. We review the main models used to study breast CSCs and how they challenge the CSC hypothesis.
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Literature
1.
Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, et al: Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008, 100: 672-679. 10.1093/jnci/djn123.CrossRefPubMed
2.
Phillips TM, McBride WH, Pajonk F: The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst. 2006, 98: 1777-1785.CrossRefPubMed
3.
Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al: let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007, 131: 1109-1123. 10.1016/j.cell.2007.10.054.CrossRefPubMed
4.
Dean M, Fojo T, Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 2005, 5: 275-284. 10.1038/nrc1590.CrossRefPubMed
5.
Hambardzumyan D, Squatrito M, Holland EC: Radiation resistance and stem-like cells in brain tumors. Cancer Cell. 2006, 10: 454-456. 10.1016/j.ccr.2006.11.008.CrossRefPubMed
6.
Duester G: Families of retinoid dehydrogenases regulating vitamin A function: production of visual pigment and retinoic acid. Eur J Biochem. 2000, 267: 4315-4324. 10.1046/j.1432-1327.2000.01497.x.CrossRefPubMed
7.
Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, et al: A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 2004, 101: 14228-14233. 10.1073/pnas.0400067101.CrossRefPubMedPubMedCentral
8.
Minn AJ, Gupta GP, Padua D, Bos P, Nguyen DX, Nuyten D, et al: Lung metastasis genes couple breast tumor size and metastatic spread. Proc Natl Acad Sci USA. 2007, 104: 6740-6745. 10.1073/pnas.0701138104.CrossRefPubMedPubMedCentral
9.
Montanaro F, Liadaki K, Schienda J, Flint A, Gussoni E, Kunkel LM: Demystifying SP cell purification: viability, yield, and phenotype are defined by isolation parameters. Exp Cell Res. 2004, 298: 144-154. 10.1016/j.yexcr.2004.04.010.CrossRefPubMed
10.
Setoguchi T, Taga T, Kondo T: Cancer stem cells persist in many cancer cell lines. Cell Cycle. 2004, 3: 414-415.CrossRefPubMed
11.
Clayton H, Titley I, Vivanco M: Growth and differentiation of progenitor/stem cells derived from the human mammary gland. Exp Cell Res. 2004, 297: 444-460. 10.1016/j.yexcr.2004.03.029.CrossRefPubMed
12.
Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, et al: In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 2003, 17: 1253-1270. 10.1101/gad.1061803.CrossRefPubMedPubMedCentral
13.
Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA: Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol. 2002, 245: 42-56. 10.1006/dbio.2002.0625.CrossRefPubMed
14.
Alvi AJ, Clayton H, Joshi C, Enver T, Ashworth A, Vivanco MM, et al: Functional and molecular characterisation of mammary side population cells. Breast Cancer Res. 2003, 5: R1-R8. 10.1186/bcr563.CrossRefPubMed
15.
Kondo T, Setoguchi T, Taga T: Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA. 2004, 101: 781-786. 10.1073/pnas.0307618100.CrossRefPubMedPubMedCentral
16.
Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG: Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and A. Cancer Res. 2005, 65: 6207-6219. 10.1158/0008-5472.CAN-05-0592.CrossRefPubMed
17.
Ho MM, Ng AV, Lam S, Hung JY: Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007, 67: 4827-4833. 10.1158/0008-5472.CAN-06-3557.CrossRefPubMed
18.
Pearce DJ, Bonnet D: The combined use of Hoechst efflux ability and aldehyde dehydrogenase activity to identify murine and human hematopoietic stem cells. Exp Hematol. 2007, 35: 1437-1446. 10.1016/j.exphem.2007.06.002.CrossRefPubMed
19.
Al Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003, 100: 3983-3988. 10.1073/pnas.0530291100.CrossRefPubMedPubMedCentral
20.
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al: ALDH1 Is a Marker of Normal and Malignant Human Mammary Stem Cells and a Predictor of Poor Clinical Outcome. Cell Stem Cell. 2007, 1: 555-567. 10.1016/j.stem.2007.08.014.CrossRefPubMedPubMedCentral
21.
Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007, 104: 10158-10163. 10.1073/pnas.0703478104.CrossRefPubMedPubMedCentral
22.
Harper LJ, Piper K, Common J, Fortune F, Mackenzie IC: Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J Oral Pathol Med. 2007, 36: 594-603.CrossRefPubMed
23.
Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 2007, 104: 973-978. 10.1073/pnas.0610117104.CrossRefPubMedPubMedCentral
24.
Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE: Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006, 12: 1167-1174. 10.1038/nm1483.CrossRefPubMed
25.
Subramaniam V, Vincent IR, Gilakjan M, Jothy S: Suppression of human colon cancer tumors in nude mice by siRNA CD44 gene therapy. Exp Mol Pathol. 2007, 83: 332-340. 10.1016/j.yexmp.2007.08.013.CrossRefPubMed
26.
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al: Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67: 1030-1037. 10.1158/0008-5472.CAN-06-2030.CrossRefPubMed
27.
Kleer CG, Zhang Y, Merajver SD: CCN6 (WISP3) as a new regulator of the epithelial phenotype in breast cancer. Cells Tissues Organs. 2007, 185: 95-99. 10.1159/000101308.CrossRefPubMed
28.
Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, et al: Purification and unique properties of mammary epithelial stem cells. Nature. 2006, 439: 993-997.PubMed
29.
Cariati M, Naderi A, Brown JP, Smalley MJ, Pinder SE, Caldas C, et al: Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line. Int J Cancer. 2008, 122: 298-304. 10.1002/ijc.23103.CrossRefPubMed
30.
Sleeman KE, Kendrick H, Robertson D, Isacke CM, Ashworth A, Smalley MJ: Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. J Cell Biol. 2007, 176: 19-26. 10.1083/jcb.200604065.CrossRefPubMedPubMedCentral
31.
Clarke RB, Anderson E, Howell A, Potten CS: Regulation of human breast epithelial stem cells. Cell Prolif. 2003, 36 (Suppl 1): 45-58. 10.1046/j.1365-2184.36.s.1.5.x.CrossRefPubMed
32.
Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L: Brca1 breast tumors contain distinct CD44+/. Breast Cancer Res. 2008, 10: R10-10.1186/bcr1855.CrossRefPubMedPubMedCentral
33.
O'Brien CA, Pollett A, Gallinger S, Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007, 445: 106-110. 10.1038/nature05372.CrossRefPubMed
34.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al: Identification and expansion of human colon-cancer-initiating cells. Nature. 2007, 445: 111-115. 10.1038/nature05384.CrossRefPubMed
35.
Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al: Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003, 63: 5821-5828.PubMed
36.
Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, et al: Generation of a functional mammary gland from a single stem cell. Nature. 2006, 439: 84-88. 10.1038/nature04372.CrossRefPubMed
37.
Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, et al: Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol. 2007, 9: 201-209. 10.1038/ncb1530.CrossRefPubMed
38.
Vaillant F, Asselin-Labat ML, Shackleton M, Forrest NC, Lindeman GJ, Visvader JE: The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res. 2008, 68: 7711-7717. 10.1158/0008-5472.CAN-08-1949.CrossRefPubMed
39.
Sophos NA, Vasiliou V: Aldehyde dehydrogenase gene superfamily: the 2002 update. Chem Biol Interact. 2003, 143–144: 5-22. 10.1016/S0009-2797(02)00163-1.CrossRefPubMed
40.
Armstrong L, Stojkovic M, Dimmick I, Ahmad S, Stojkovic P, Hole N, et al: Phenotypic characterization of murine primitive hematopoietic progenitor cells isolated on basis of aldehyde dehydrogenase activity. Stem Cells. 2004, 22: 1142-1151. 10.1634/stemcells.2004-0170.CrossRefPubMed
41.
Hess DA, Meyerrose TE, Wirthlin L, Craft TP, Herrbrich PE, Creer MH, et al: Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood. 2004, 104: 1648-1655. 10.1182/blood-2004-02-0448.CrossRefPubMed
42.
Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R, et al: Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood. 2006, 107: 2162-2169. 10.1182/blood-2005-06-2284.CrossRefPubMedPubMedCentral
43.
Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, et al: Characterization of clonogenic multiple myeloma cells. Blood. 2004, 103: 2332-2336. 10.1182/blood-2003-09-3064.CrossRefPubMed
44.
Pearce DJ, Taussig D, Simpson C, Allen K, Rohatiner AZ, Lister TA, et al: Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells. 2005, 23: 752-760. 10.1634/stemcells.2004-0292.CrossRefPubMed
45.
Corti S, Locatelli F, Papadimitriou D, Donadoni C, Salani S, Del Bo R, et al: Identification of a primitive brain-derived neural stem cell population based on aldehyde dehydrogenase activity. Stem Cells. 2006, 24: 975-985. 10.1634/stemcells.2005-0217.CrossRefPubMed
46.
Ucar D, Cogle CR, Zucali JR, Ostmark B, Scott EW, Zori R, et al: Aldehyde dehydrogenase activity as a functional marker for lung cancer. Chem Biol Interact. 2009, 178: 48-55. 10.1016/j.cbi.2008.09.029.CrossRefPubMed
47.
Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA, et al: High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med. 2008.
48.
Levi BP, Yilmaz OH, Duester G, Morrison SJ: Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. Blood. 2009, 113: 1670-1680. 10.1182/blood-2008-05-156752.CrossRefPubMedPubMedCentral
49.
Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H: Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005, 11: 1154-1159.PubMed
50.
Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P, et al: The clinicopathologic and prognostic significance of CD44+/CD24(-/low) and CD44-/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol. 2008, 39: 1096-1102. 10.1016/j.humpath.2007.12.003.CrossRefPubMed
51.
52.
Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, et al: Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006, 12: 5615-5621. 10.1158/1078-0432.CCR-06-0169.CrossRefPubMed
53.
54.
Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS: Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res. 2004, 6: R605-R615. 10.1186/bcr920.CrossRefPubMedPubMedCentral
55.
Dontu G, El Ashry D, Wicha MS: Breast cancer, stem/progenitor cells and the estrogen receptor. Trends in Endocrinology and Metabolism. 2004, 15: 193-197. 10.1016/j.tem.2004.05.011.CrossRefPubMed
56.
Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson NG, et al: Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst. 2007, 99: 616-627. 10.1093/jnci/djk133.CrossRefPubMed
57.
Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005, 65: 5506-5511. 10.1158/0008-5472.CAN-05-0626.CrossRefPubMed
58.
Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, et al: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006, 10: 515-527. 10.1016/j.ccr.2006.10.008.CrossRefPubMedPubMedCentral
59.
Seo DC, Sung JM, Cho HJ, Yi H, Seo KH, Choi IS, et al: Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells. Mol Cancer. 2007, 6: 75-10.1186/1476-4598-6-75.CrossRefPubMedPubMedCentral
60.
Fillmore CM, Kuperwasser C: Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res. 2008, 10: R25-10.1186/bcr1982.CrossRefPubMedPubMedCentral
61.
Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, et al: Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 2009, 69: 1302-1313. 10.1158/0008-5472.CAN-08-2741.CrossRefPubMedPubMedCentral
62.
Boven E, Winograd B, Berger DP, Dumont MP, Braakhuis BJ, Fodstad O, et al: Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study. Cancer Res. 1992, 52: 5940-5947.PubMed
63.
Mattern J, Bak M, Hahn EW, Volm M: Human tumor xenografts as model for drug testing. Cancer Metastasis Rev. 1988, 7: 263-284. 10.1007/BF00047755.CrossRefPubMed
64.
Outzen HC, Custer RP: Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse. J Natl Cancer Inst. 1975, 55: 1461-1466.PubMed
65.
Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, et al: Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA. 2004, 101: 4966-4971. 10.1073/pnas.0401064101.CrossRefPubMedPubMedCentral
66.
Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A: Tumor growth need not be driven by rare cancer stem cells. Science. 2007, 317: 337-10.1126/science.1142596.CrossRefPubMed
67.
Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ: Efficient tumour formation by single human melanoma cells. Nature. 2008, 456: 593-598. 10.1038/nature07567.CrossRefPubMedPubMedCentral
Metadata
Title
Breast cancer stem cells: tools and models to rely on
Authors
Emmanuelle Charafe-Jauffret
Christophe Ginestier
Daniel Birnbaum
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-202

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