Document Detail


Permanently blocked stem cells derived from breast cancer cell lines.
MedLine Citation:
PMID:  20506227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Gangadharan B Sajithlal; Kristi Rothermund; Fang Zhang; David J Dabbs; Jean J Latimer; Stephen G Grant; Edward V Prochownik
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  28     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-16     Completed Date:  2010-09-13     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1008-18     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology
Biological Markers / analysis
Breast Neoplasms / chemistry,  genetics,  pathology*
Cell Culture Techniques / methods*
Cell Differentiation
Cell Line, Tumor
Humans
Neoplastic Stem Cells / chemistry,  cytology*,  drug effects,  metabolism
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
CA78259/CA/NCI NIH HHS; R29 CA071894/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Biological Markers

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