Document Detail

Glioma cell populations grouped by different cell type markers drive brain tumor growth.
MedLine Citation:
PMID:  20460538     Owner:  NLM     Status:  MEDLINE    
Although CD133 has been proposed as a marker for brain tumor-initiating cells, studies show that a tumorigenic potential exists among CD133(-) glioma cells as well. However, it is not established whether the ability of CD133(-) cells to form tumors is a property confined to a small subpopulation, rather than a common trait associated with most glioma cell types. Thus, we used lentiviral vectors expressing green fluorescent protein under lineage-specific promoters to identify CD133(-) glioma cells expressing Nestin, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE). Flow cytometry analysis showed the presence of CD133(-) subpopulations expressing these markers in glioma cell lines and in primary cultures from human glioblastoma (GBM) biopsies. Moreover, analysis of cell cycle distribution showed that subgroups expressing Nestin, GFAP, and NSE uniformly contained actively cycling cells, when cultured in serum-containing medium and stem cell medium. These subpopulations were fluorescence-activated cell sorted from CD133(-) U373 glioma cells and implanted intracerebrally in severe combined immunodeficient mice. Moreover, we implanted Nestin-, GFAP-, and NSE-positive glioma cells sorted from a human GBM biopsy, following removal of CD133-positive cells. All the CD133(-) subpopulations produced tumors, with no significant differences in survival or tumor take rates. However, there was a trend toward lower take rates for CD133(-) glioma subpopulations expressing GFAP and NSE. These findings suggest that the ability to form tumors may be a general trait associated with different glioma cell phenotypes, rather than a property limited to an exclusive subpopulation of glioma stem cells.
Lars Prestegarden; Agnete Svendsen; Jian Wang; Linda Sleire; Kai Ove Skaftnesmo; Rolf Bjerkvig; Tao Yan; Lasse Askland; Andreas Persson; Per ?ystein Sakariassen; Per ?yvind Enger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-11
Journal Detail:
Title:  Cancer research     Volume:  70     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-02     Completed Date:  2010-06-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4274-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 AACR.
Oncomatrix Research Lab, Department of Biomedicine and Norlux Neuro-Oncology, Department of Biomedicine, University of Bergen, Bergen, Norway.
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MeSH Terms
Antigens, CD / biosynthesis
Brain Neoplasms / classification,  metabolism*,  pathology*
Cell Growth Processes / physiology
Cell Line, Tumor
Genetic Vectors
Glial Fibrillary Acidic Protein / biosynthesis,  genetics
Glioblastoma / classification,  metabolism*,  pathology*
Glycoproteins / biosynthesis
Green Fluorescent Proteins / biosynthesis,  genetics
Intermediate Filament Proteins / biosynthesis,  genetics
Lentivirus / genetics
Mice, SCID
Nerve Tissue Proteins / biosynthesis,  genetics
Phosphopyruvate Hydratase / biosynthesis,  genetics
Tumor Markers, Biological / biosynthesis*
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/Glial Fibrillary Acidic Protein; 0/Glycoproteins; 0/Intermediate Filament Proteins; 0/Nerve Tissue Proteins; 0/Peptides; 0/Tumor Markers, Biological; 0/nestin; 147336-22-9/Green Fluorescent Proteins; EC Hydratase

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