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Cancer Stem Cells
Article first published online: 9 APR 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 5, pages 833–844, May 2012
How to Cite
Lagadec, C., Vlashi, E., Della Donna, L., Dekmezian, C. and Pajonk, F. (2012), Radiation-Induced Reprogramming of Breast Cancer Cells. STEM CELLS, 30: 833–844. doi: 10.1002/stem.1058
Author contributions: C.L.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; E.V.: conception and design and data analysis and interpretation; L.D.D.: conception and design; C.D.: collection and assembly of data; F.P.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript, and financial support.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS February 10, 2012.
- Issue published online: 9 APR 2012
- Article first published online: 9 APR 2012
- Accepted manuscript online: 10 FEB 2012 11:08AM EST
- Manuscript Accepted: 29 JAN 2012
- Manuscript Revised: 26 JAN 2012
- Manuscript Received: 4 AUG 2011
- Breast cancer stem cells;
Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs) able to regrow a tumor while their progeny lack this ability. Recently, several groups reported enrichment for BCSCs when breast cancers were subjected to classic anticancer treatment. However, the underlying mechanisms leading to this enrichment are incompletely understood. Using non-BCSCs sorted from patient samples, we found that ionizing radiation reprogrammed differentiated breast cancer cells into induced BCSCs (iBCSCs). iBCSCs showed increased mammosphere formation, increased tumorigenicity, and expressed the same stemness-related genes as BCSCs from nonirradiated samples. Reprogramming occurred in a polyploid subpopulation of cells, coincided with re-expression of the transcription factors Oct4, sex determining region Y-box 2, Nanog, and Klf4, and could be partially prevented by Notch inhibition. We conclude that radiation may induce a BCSC phenotype in differentiated breast cancer cells and that this mechanism contributes to increased BCSC numbers seen after classic anticancer treatment. STEM CELLS 2012;30:833–844