title: CD133+ niches and single cells in glioblastoma have different phenotypes.
abstract: Putative CD133(+) brain tumor stem cells have been shown to be located in niches and as single cells. This is the first study providing insight into the different phenotypes of CD133(+) cells in glioblastoma according to localization. Paraffin sections were stained by double immunofluorescence with CD133 and the candidate stem cell markers Sox2, Bmi-1, EGFR, podoplanin and nestin, the proliferation marker Ki67 and the endothelial cell markers CD31, CD34, and VWF. Cell counting showed that the CD133(+) cells in the niches had a significantly higher expression of Sox2, EGFR and nestin compared to CD133(+) single cells, but only a 3% Ki67 labeling index versus 14% found for CD133(+) single cells. Only low endothelial cell marker expression was found in the niches or the CD133(-) tumor areas, while 43% CD133(+)/CD31(+) and 25% CD133(+)/CD34(+) single cells were found. CD133(+) blood vessels within CD133(+) niches were less proliferative and more often Bmi-1(+) than CD133(+) blood vessels outside niches. In conclusion, different CD133(+) cell phenotypes exist according to the in situ localization, and also the phenotype of CD133(+) blood vessels vary according to the localization. CD133(+) niches contain stem-like cells with a lower proliferation index than CD133(+) single cells, which have an endothelial differentiation profile suggesting a role in angiogenesis.
authors.affiliation: Department of Pathology, Odense University Hospital, Winsløwparken 15, 5000 Odense C, Denmark.
authors.forename: Karina
authors.initials: K
authors.lastname: Christensen
authors.forename: Henrik Daa
authors.initials: HD
authors.lastname: Schrøder
authors.forename: Bjarne Winther
authors.initials: BW
authors.lastname: Kristensen
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D001932:Brain Neoplasms / Q000473:pathology*; D002452:Cell Count / Q000379:methods; D005260:Female; D005909:Glioblastoma / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C069077:BMI1 protein, human; D006023:Glycoproteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C028254:von Willebrand factor receptor; D063150:Polycomb Repressive Complex 1