BACKGROUND: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. METHODS: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy. RESULTS: CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate. CONCLUSIONS: Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer.

] Dundee Cancer Centre University of Dundee Ninewells Hospital and Medical School Dundee DD1 9SY UK [2]

] Dundee Cancer Centre University of Dundee Ninewells Hospital and Medical School Dundee DD1 9SY UK [2] Department of Surgical Oncology MD Anderson Cancer Center Houston TX 77030 USA

Dundee Cancer Centre University of Dundee Ninewells Hospital and Medical School Dundee DD1 9SY UK

Regional Centre for Applied Molecular Oncology Department of Oncological and Experimental Pathology Masaryk Memorial Cancer Institute 656 53 Brno Czech Republic

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