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Characterization of mammary cancer stem cells in the MMTV-PyMT mouse model.
MedLine Citation:
PMID:  22878936     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Breast cancer stem cells, the root of tumor growth, present challenges to investigate: Primary human breast cancer cells are difficult to establish in culture and inconsistently yield tumors after transplantation into immune-deficient recipient mice. Furthermore, there is limited characterization of mammary cancer stem cells in mice, the ideal model for the study of breast cancer. We herein describe a pre-clinical breast cancer stem cell model, based on the properties of cancer stem cells, derived from transgenic MMTV-PyMT mice. Using a defined set of cell surface markers to identify cancer stem cells by flow cytometry, at least four cell populations were recovered from primary mammary cancers. Only two of the four populations, one epithelial and one mesenchymal, were able to survive and proliferate in vitro. The epithelial population exhibited tumor initiation potential with as few as 10 cells injected into syngeneic immune-competent recipients. Tumors initiated from injected cell lines recapitulated the morphological and physiological components of the primary tumor. To highlight the stemness potential of the putative cancer stem cells, B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) expression was knocked down via shRNA targeting Bmi-1. Without Bmi-1 expression, putative cancer stem cells could no longer initiate tumors, but tumor initiation was rescued with the introduction of a Bmi-1 overexpression vector in the Bmi-1 knockdown cells. In conclusion, our data show that primary mammary cancers from MMTV-PyMT mice contain putative cancer stem cells that survive in culture and can be used to create a model for study of mammary cancer stem cells.
Authors:
Jun Ma; Denise Grant Lanza; Ian Guest; Chang Uk-Lim; Anna Glinskii; Gennadi Glinsky; Stewart Sell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-10
Journal Detail:
Title:  Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine     Volume:  -     ISSN:  1423-0380     ISO Abbreviation:  Tumour Biol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8409922     Medline TA:  Tumour Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Translational and Functional Genomics Laboratory, Ordway Research Institute, Albany, NY, 12208, USA.
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