Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44(hi/)CD24 (lo/-) stem cell phenotype in human breast cancer.
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.
Invasion and Metastasis Unit, St. Vincent's Institute, 9 Princes St, Fitzroy, Melbourne 3065, Australia.
Tony
T
Blick
Honor
H
Hugo
Edwin
E
Widodo
Mark
M
Waltham
Cletus
C
Pinto
Sendurai A
SA
Mani
Robert A
RA
Weinberg
Richard M
RM
Neve
Marc E
ME
Lenburg
Erik W
EW
Thompson
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051927:CD24 Antigen / Q000378:metabolism*; D054337:Cell Dedifferentiation; D045744:Cell Line, Tumor; D054338:Cell Transdifferentiation; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype
D000970:Antineoplastic Agents; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors