Lack of correlation of stem cell markers in breast cancer stem cells

Br J Cancer. 2014 Apr 15;110(8):2063-71. doi: 10.1038/bjc.2014.105. Epub 2014 Feb 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • CD24 Antigen / biosynthesis
  • CD24 Antigen / immunology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Hyaluronan Receptors / immunology
  • MCF-7 Cells
  • Neoplastic Stem Cells / metabolism*
  • SOXB1 Transcription Factors / biosynthesis
  • SOXB1 Transcription Factors / immunology
  • Xenograft Model Antitumor Assays

Substances

  • CD24 Antigen
  • CD44 protein, human
  • Hyaluronan Receptors
  • SOX2 protein, human
  • SOXB1 Transcription Factors