Epithelial Mesenchymal Transition Traits in Human Breast Cancer Cell Lines Parallel the CD44hi/CD24lo/- Stem Cell Phenotype in Human Breast Cancer

  • Tony Blick
  • Honor Hugo
  • Edwin Widodo
  • Mark Waltham
  • Cletus Pinto
  • Sendurai A. Mani
  • Robert A. Weinberg
  • Richard M. Neve
  • Marc E. Lenburg
  • Erik W. ThompsonEmail author


We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties (‘Basal B’/Mesenchymal), distinct from subgroups with either predominantly luminal (‘Luminal’) or mixed basal/luminal (‘Basal A’) features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44highCD24low. Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.


EMT Basal B Mesenchymal Breast cancer Breast cancer stem cell CD24 



Aldehyde dehydrogenase 1 family, member A1


Breast cancer stem cells


Breast cancer 1, early onset

C/EBP β-2

CCAAT/enhancer binding protein (C/EBP), beta






Circulating tumor cells


Discoidin domain receptor tyrosine kinase 1


Disseminated tumor cells


Epidermal growth factor


Epithelial-to-mesenchymal transition




Epithelial membrane protein 3


Estrogen receptor


Endothelial-to-mesenchymal transition


Focal adhesion kinase


Fos-like antigen


Growth arrest-specific 6


Human exonic evidence based oligonucleotide array


Homeobox B7


Human mammary epithelial cells


Hazard recurrence


Mammary stem cells


Mammary epithelial cells


Mesenchymal-to-epithelial transition


Messenger RNA


Nuclear factor kappa B


Phosphoglucose isomerise/autocrine motility factor


Protein C receptor, endothelial (EPCR)


Short hairpin ribonucleic acid


Src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)


Transforming growth factor-beta



The research effort associated with this article was funded in part by the U.S. Army Medical Research and Materiel Command (BC0213201 and BC084667), the Victorian Breast Cancer Research Consortium, The Cancer Council Victoria (#509295) and the National Breast Cancer Foundation (Australia). TB and EWT were supported in part by the Victorian Breast Cancer Research Consortium. HH is supported by a fellowship from the National Breast Cancer Foundation, Australia. EW is the recipient of an AUS Aid Scholarship. Parts of this work were also supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research (Contract DE-AC03-76SF00098) and the California Breast Cancer Research Program (CBCRP) grant # 7FB-0027. SAM lab is supported by V foundations V Scholar award and M. D. Anderson Research Trust Fellow award. RAW is supported in part by the Breast Cancer Research Foundation. The authors are grateful to Dr. Kornelia Polyak for providing prepublication data from the Shipitsin et al. study (2007) for comparative analysis.

Supplementary material

10911_2010_9175_MOESM1_ESM.xls (20 kb)
Supplementary Table 1 The literature pertaining to EMT in breast cancer was searched and molecules shown empirically to cause EMT or change during EMT were assembled. In some cases, additional family members were included. Gene products known to be differentially expressed across different breast cancer cell lines were not included on the basis of that alone. Although not comprehensive, EMT-SIG is an ad hoc, literature-derived gene list from the breast cancer literature. (XLS 20 kb)


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Tony Blick
    • 1
  • Honor Hugo
    • 1
  • Edwin Widodo
    • 2
    • 3
  • Mark Waltham
    • 1
    • 2
  • Cletus Pinto
    • 1
    • 2
  • Sendurai A. Mani
    • 4
  • Robert A. Weinberg
    • 5
  • Richard M. Neve
    • 6
    • 7
  • Marc E. Lenburg
    • 7
    • 8
  • Erik W. Thompson
    • 1
    • 2
    Email author
  1. 1.Invasion and Metastasis UnitSt. Vincent’s InstituteMelbourneAustralia
  2. 2.Department of SurgerySt. Vincent’s Hospital, University of MelbourneFitzroyAustralia
  3. 3.Faculty of MedicineBrawijaya UniversityEast JavaIndonesia
  4. 4.Department of Molecular Pathology, Unit 951The University of Texas M. D. Anderson Cancer CenterHoustonUSA
  5. 5.Whitehead Institute for Biomedical Research, 9 Cambridge Center, and Department of BiologyMassachusetts Institute of TechnologyCambridgeUSA
  6. 6.Molecular Biology DepartmentGenentech IncSouth San FranciscoUSA
  7. 7.Life Sciences DivisionLawrence Berkeley National LaboratoryBerkeleyUSA
  8. 8.Department of Pathology and Laboratory MedicineBoston University School of MedicineBostonUSA

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