CD133+ and nestin+ tumor-initiating cells dominate in N29 and N32 experimental gliomas.
The current study was designed to critically evaluate the notion that cancer stem cell (CSC)-like cells constitute a subpopulation of cells within experimental gliomas. Virtually all cells within the N29 and N32 rat glioma models homogenously expressed CD133, the stem/progenitor marker nestin as well as the neural lineage markers glial fibrillary acidic protein, betaIII-tubulin, and CNPase in vitro. The phenotype was largely retained on exposure to conditions promoting differentiation in vitro and after intracranial implantation of tumor cells into syngeneic hosts. Unsorted adherently grown cells displayed very high clonogenicity in vitro and robust tumorigenicity in vivo. Single N29 and N32 tumor cells invariably formed clones in vitro, and intracerebral inoculation of as few as 10 adherently growing N29 and N32 tumor cells, respectively, gave rise to a tumor. These results provide an alternative view on CSC-like cells in glioma models: sphere-formation is not a prerequisite for accumulation of tumorigenic cells, and CSC-like cells do not reside within a rare subpopulation of cells in these glioma models. N29 and N32 gliomas may accordingly be used for the development of treatment strategies directed specifically against a practically pure population of brain tumor-initiating CSC-like cells.
Bexell
Daniel
D
Department of Clinical Sciences, Division of Neurosurgery,The Rausing Laboratory, BMC D14, Lund University, Lund, Sweden. daniel.bexell@med.lu.se
Gunnarsson
Salina
S
Siesjö
Peter
P
Bengzon
Johan
J
Darabi
Anna
A
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D010455:Peptides; C000606025:Prom1 protein, rat