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

Abstract

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.

• Authors: Suling Liu, Yang Cong, Dong Wang, Yu Sun, Lu Deng, Yajing Liu, Rachel Martin-Trevino, Li Shang, Sean P McDermott, Melissa D Landis, Suhyung Hong, April Adams, Rosemarie D'Angelo, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Shawn G Clouthier, Daniel Birnbaum, Stephen T Wong, Ming Zhan, Jenny C Chang, Max S Wicha
• Journal: Stem cell reports (Stem Cell Reports) Vol. 2 Issue 1 Pg. 78-91 (Jan 14 2014) ISSN: 2213-6711 [Print] United States
• PMID: 24511467 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CD24 Antigen
• Hyaluronan Receptors
• Aldehyde Dehydrogenase

Topics

• Aldehyde Dehydrogenase (metabolism)
• Breast Neoplasms (metabolism, pathology)
• CD24 Antigen (metabolism)
• Epithelial Cells (cytology)
• Epithelial-Mesenchymal Transition
• Female
• Humans
• Hyaluronan Receptors (metabolism)
• MCF-7 Cells
• Mammary Glands, Human (cytology, metabolism)
• Mesenchymal Stem Cells (cytology)
• Neoplastic Stem Cells (cytology, metabolism)
• Transcriptome