Document Detail

Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis.
MedLine Citation:
PMID:  22585577     Owner:  NLM     Status:  MEDLINE    
Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have increased resistance to conventional therapies and are capable of establishing metastasis. However, only a few biomarkers of CSCs have been identified. Here, we report that ganglioside GD2 (a glycosphingolipid) identifies a small fraction of cells in human breast cancer cell lines and patient samples that are capable of forming mammospheres and initiating tumors with as few as 10 GD2+ cells. In addition, the majority of GD2+ cells are also CD44hiCD24lo, the previously established CSC-associated cell surface phenotype. Gene expression analysis revealed that GD3 synthase (GD3S) is highly expressed in GD2+ as well as in CD44hiCD24lo cells and that interference with GD3S expression, either by shRNA or using a pharmacological inhibitor, reduced the CSC population and CSC-associated properties. GD3S knockdown completely abrogated tumor formation in vivo. Also, induction of epithelial-mesenchymal transition (EMT) in transformed human mammary epithelial cells (HMLER cells) dramatically increased GD2 as well as GD3S expression in these cells, suggesting a role of EMT in the origin of GD2+ breast CSCs. In summary, we identified GD2 as a new CSC-specific cell surface marker and GD3S as a potential therapeutic target for CSCs, with the possibility of improving survival and cure rates in patients with breast cancer.
Venkata Lokesh Battula; Yuexi Shi; Kurt W Evans; Rui-Yu Wang; Erika L Spaeth; Rodrigo O Jacamo; Rudy Guerra; Aysegul A Sahin; Frank C Marini; Gabriel Hortobagyi; Sendurai A Mani; Michael Andreeff
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-15
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-08-20     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2066-78     Citation Subset:  AIM; IM    
Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
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MeSH Terms
Antigens, CD24 / genetics,  metabolism
Antigens, CD44 / genetics,  metabolism
Breast Neoplasms / genetics,  metabolism*,  pathology
Cell Line, Transformed
Cell Line, Tumor
Epithelial-Mesenchymal Transition / genetics
Gangliosides / biosynthesis*,  genetics
Gene Expression Regulation, Enzymologic / genetics
Gene Expression Regulation, Neoplastic / genetics
Gene Knockdown Techniques
Mice, Inbred NOD
Mice, SCID
Neoplasm Proteins / genetics,  metabolism
Neoplasm Transplantation
Neoplastic Stem Cells / metabolism*,  pathology,  transplantation
Sialyltransferases / biosynthesis,  genetics
Transplantation, Heterologous
Tumor Markers, Biological / biosynthesis*,  genetics
Grant Support
Reg. No./Substance:
0/Antigens, CD24; 0/Antigens, CD44; 0/CD24 protein, human; 0/Gangliosides; 0/Neoplasm Proteins; 0/Tumor Markers, Biological; 65988-71-8/ganglioside, GD2; EC 2.4.99.-/Sialyltransferases; EC alpha-2,8-sialyltransferase

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