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 CD44(high)CD24(low). 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.

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Dynamic interconversions between transitional epithelial and mesenchymal states underpin the epithelial mesenchymal plasticity (EMP) seen in some carcinoma cell systems. We have delineated epithelial and mesenchymal subpopulations existing within the PMC42-LA breast cancer cell line by their EpCAM expression. These purified but phenotypically plastic states, EpCAMHigh (epithelial) and EpCAMLow (mesenchymal), have the ability to regain the phenotypic equilibrium of the parental population (i.e., 80% epithelial and 20% mesenchymal) over time, although the rate of reversion in the mesenchymal direction (epithelial-mesenchymal transition; EMT) is higher than that in the epithelial direction (mesenchymal-epithelial transition; MET). Single-cell clonal propagation was implemented to delineate the molecular and cellular features of this intrinsic heterogeneity with respect to EMP flux. The dynamics of the phenotypic proportions of epithelial and mesenchymal states in single-cell generated clones revealed clonal diversity and intrinsic plasticity. Single cell-derived clonal progenies displayed differences in their functional attributes of proliferation, stemness marker (CD44/CD24), migration, invasion and chemo-sensitivity. Interrogation of genomic copy number variations (CNV) with whole exome sequencing (WES) in the context of chromosome count from metaphase spread indicated that chromosomal instability was not influential in driving intrinsic phenotypic plasticity. Overall, these findings reveal the stochastic nature of both the epithelial and mesenchymal subpopulations, and the single cell-derived clones for differential functional attributes.