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Stem Cell Reports. 2013 Dec 27;2(1):78-91. doi: 10.1016/j.stemcr.2013.11.009. eCollection 2014 Jan 14.

Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.

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School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Methodist Cancer Center, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 INSERM/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille 13273, France.


Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24(-)CD44(+) are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites.

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