TY - JOUR
T1 - Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts
AU - Liu, Suling
AU - Cong, Yang
AU - Wang, Dong
AU - Sun, Yu
AU - Deng, Lu
AU - Liu, Yajing
AU - Martin-Trevino, Rachel
AU - Shang, Li
AU - McDermott, Sean P.
AU - Landis, Melissa D.
AU - Hong, Suhyung
AU - Adams, April
AU - D'Angelo, Rosemarie
AU - Ginestier, Christophe
AU - Charafe-Jauffret, Emmanuelle
AU - Clouthier, Shawn G.
AU - Birnbaum, Daniel
AU - Wong, Stephen T.
AU - Zhan, Ming
AU - Chang, Jenny C.
AU - Wicha, Max S.
N1 - Funding Information:
We thank Dr. Stephen Ethier for generously providing the breast cancer cell lines SUM149 and SUM159. We also thank the University of Michigan Flow Cytometry Core, Microarray Core (Joe Washburn and Craig Johnson), Vector Core, Molecular Imaging Core, and Pathology Core for invaluable assistance. This work was supported by CAS Stem Cell grant XDA01040410 and NSFC grant 81322033 (S.L.), NIH grants CA66233 and CA101860 (M.S.W.), and NIH grant U54CA149169 (S.T.W.). M.S.W. holds equity in OncoMed Pharmaceuticals, receives research support from MedImmune and Dompe, and is a scientific advisor to MedImmune, Verastem, Cerulean, and Paganini.
PY - 2014/1/14
Y1 - 2014/1/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84892619683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892619683&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2013.11.009
DO - 10.1016/j.stemcr.2013.11.009
M3 - Article
C2 - 24511467
AN - SCOPUS:84892619683
SN - 2213-6711
VL - 2
SP - 78
EP - 91
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -