Document Detail


Lectins identify glycan biomarkers on glioblastoma-derived cancer stem cells.
MedLine Citation:
PMID:  22435486     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. Despite aggressive therapy with surgery, radiotherapy, and chemotherapy, nearly all patients succumb to disease within 2 years. Several studies have supported the presence of stem-like cells in brain tumor cultures that are CD133-positive, are capable of self-renewal, and give rise to all cell types found within the tumor, potentially perpetuating growth. CD133 is a widely accepted marker for glioma-derived cancer stem cells; however, its reliability has been questioned, creating a need for other identifiers of this biologically important subpopulation. We used a panel of 20 lectins to identify differences in glycan expression found in the glycocalyx of undifferentiated glioma-derived stem cells and differentiated cells that arise from them. Fluorescently labeled lectins that specifically recognize α-N-acetylgalactosamine (GalNAc) and α-N-acetylglucosamine (GlcNAc) differentially bound to the cell surface based on the state of cellular differentiation. GalNAc and GlcNAc were highly expressed on the surface of undifferentiated cells and showed markedly reduced expression over a 12-day duration of differentiation. Additionally, the GalNAc-recognizing lectin Dolichos biflorus agglutinin was capable of specifically selecting and sorting glioma-derived stem cell populations from an unsorted tumor stock and this subpopulation had proliferative properties similar to CD133(+) cells in vitro and also had tumor-forming capability in vivo. Our preliminary results on a single cerebellar GBM suggest that GalNAc and GlcNAc are novel biomarkers for identifying glioma-derived stem cells and can be used to isolate cancer stem cells from unsorted cell populations, thereby creating new cell lines for research or clinical testing.
Authors:
Carol Tucker-Burden; Prasanthi Chappa; Malini Krishnamoorthy; Brian A Gerwe; Christopher D Scharer; Jamie Heimburg-Molinaro; Wayne Harris; Sümeyra Naz Usta; Carmen D Eilertson; Constantinos G Hadjipanayis; Steven L Stice; Daniel J Brat; Rodney J Nash
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-27
Journal Detail:
Title:  Stem cells and development     Volume:  21     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-31     Completed Date:  2013-01-23     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2374-86     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetylgalactosamine / metabolism
Acetylglucosamine / metabolism
Antigens, CD / metabolism
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Flow Cytometry
Glioblastoma / diagnosis*,  metabolism
Glycocalyx / metabolism
Glycoproteins / metabolism
Humans
Immunohistochemistry
Lectins / metabolism*
Neoplastic Stem Cells / metabolism*
Peptides / metabolism
Plant Lectins / metabolism
Polysaccharides / analysis*
Tumor Markers, Biological / analysis*
Grant Support
ID/Acronym/Agency:
CA139035/CA/NCI NIH HHS; CA149107/CA/NCI NIH HHS; R01 CA149107/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/Glycoproteins; 0/Lectins; 0/Peptides; 0/Plant Lectins; 0/Polysaccharides; 0/Tumor Markers, Biological; 0/dolichos biflorus agglutinin; KM15WK8O5T/Acetylgalactosamine; V956696549/Acetylglucosamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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