Journal
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
Volume 15, Issue 2, Pages 235-252Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10911-010-9175-z
Keywords
EMT; Basal B; Mesenchymal; Breast cancer; Breast cancer stem cell; CD24
Categories
Funding
- U.S. Army Medical Research and Materiel Command [BC0213201, BC084667]
- Victorian Breast Cancer Research Consortium
- Cancer Council Victoria [509295]
- National Breast Cancer Foundation (Australia)
- AUS
- U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research [DE-AC03-76SF00098]
- California Breast Cancer Research Program (CBCRP) [7FB-0027]
- V foundations
- M. D. Anderson Research Trust
- Breast Cancer Research Foundation
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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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