Faculty Articles
Permanently blocked stem cells derived from breast cancer cell lines
Publication Title
Stem cells
ISSN
1549-4918
Publication Date
6-1-2010
Keywords
Antineoplastic Agents, Biological Markers, Breast Neoplasms, Cell Culture Techniques, Cell Differentiation, Cell Line, Tumor, Humans, Neoplastic Stem Cells, Transcription, Genetic
Abstract
Cancer stem cells (CSCs) are thought to be resistant to standard chemotherapeutic drugs and the inimical conditions of the tumor microenvironment. Obtaining CSCs in sufficient quantities and maintaining their undifferentiated state have been major hurdles to their further characterization and to the identification of new pharmaceuticals that preferentially target these cells. We describe here the tagging of CSC-like populations from four human breast cancer cell lines with green fluorescent protein (GFP) under the control of the Oct3/4 stem cell-specific promoter. As expected, GFP was expressed by the CSC-enriched populations. However, an unanticipated result was that these cells remained blocked in a CSC-like state and tended to be resistant to chemotherapeutic drugs as well as acidotic and hypoxic conditions. These CSC-like cells possessed several other in vitro attributes of CSCs and were able to reproducibly generate tumors in immunocompromised mice from as few as 100 cells. Moreover, the tumors derived from these cells were comprised almost exclusively of pure CSCs. The ability of the Oct3/4 promoter to block CSC differentiation underscores its potential general utility for obtaining highly purified CSC populations, although the mechanism by which it does so remains undefined and subject to further study. Nonetheless, such stable cell lines should be extremely valuable tools for studying basic questions pertaining to CSC biology and for the initial identification of novel CSC-specific chemotherapeutic agents, which can then be verified in primary CSCs.
DOI
10.1002/stem.424
Volume
28
Issue
6
First Page
1008
Last Page
1018
Disciplines
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
NSUWorks Citation
Sajithlal, Gangadharan B; Rothermund, Kristi; Zhang, Fang; Dabbs, David J.; Latimer, Jean Johanna; Grant, Stephen G.; and Prochownik, Edward V., "Permanently blocked stem cells derived from breast cancer cell lines" (2010). Faculty Articles. 4.
https://nsuworks.nova.edu/hpd_corx_facarticles/4
