Journal of Mammary Gland Biology and Neoplasia

, Volume 15, Issue 2, pp 235–252

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. Thompson
Article

DOI: 10.1007/s10911-010-9175-z

Cite this article as:
Blick, T., Hugo, H., Widodo, E. et al. J Mammary Gland Biol Neoplasia (2010) 15: 235. doi:10.1007/s10911-010-9175-z

Abstract

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.

Keywords

EMT Basal B Mesenchymal Breast cancer Breast cancer stem cell CD24 

Abbreviations

ALDH1

Aldehyde dehydrogenase 1 family, member A1

BCSC

Breast cancer stem cells

BRCA1

Breast cancer 1, early onset

C/EBP β-2

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

CDH1

E-cadherin

COX-2

Cyclooxygenase-2

CTC

Circulating tumor cells

DDR1

Discoidin domain receptor tyrosine kinase 1

DTC

Disseminated tumor cells

EGF

Epidermal growth factor

EMT

Epithelial-to-mesenchymal transition

EMT-SIG

EMT-signature

EMP3

Epithelial membrane protein 3

ER

Estrogen receptor

EndMT

Endothelial-to-mesenchymal transition

FAK

Focal adhesion kinase

FOSL

Fos-like antigen

GAS6

Growth arrest-specific 6

HEEBO

Human exonic evidence based oligonucleotide array

HOXB7

Homeobox B7

HMLE

Human mammary epithelial cells

HR

Hazard recurrence

MaSC

Mammary stem cells

MEC

Mammary epithelial cells

MET

Mesenchymal-to-epithelial transition

mRNA

Messenger RNA

NFkB

Nuclear factor kappa B

PGI/AMF

Phosphoglucose isomerise/autocrine motility factor

PROCR

Protein C receptor, endothelial (EPCR)

shRNA

Short hairpin ribonucleic acid

Src

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

TGF-beta

Transforming growth factor-beta

Supplementary material

10911_2010_9175_MOESM1_ESM.xls (20 kb)
Supplementary Table 1The 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)

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
  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