title: CD133+ and Nestin+ Glioma Stem-Like Cells Reside Around CD31+ Arterioles in Niches that Express SDF-1α, CXCR4, Osteopontin and Cathepsin K.
abstract: Poor survival of high-grade glioma is at least partly caused by glioma stem-like cells (GSLCs) that are resistant to therapy. GSLCs reside in niches in close vicinity of endothelium. The aim of the present study was to characterize proteins that may be functional in the GSLC niche by performing immunohistochemistry on serial cryostat sections of human high-grade glioma samples. We have found nine niches in five out of five high-grade glioma samples that were all surrounding arterioles with CD31+ endothelial cells and containing cellular structures that were CD133+ and nestin+. All nine niches expressed stromal-derived factor-1α (SDF-1α), its receptor C-X-C chemokine receptor type 4 (CXCR4), osteopontin and cathepsin K. SDF-1α plays a role in homing of CXCR4+ stem cells and leukocytes, whereas osteopontin and cathepsin K promote migration of cancer cells and leukocytes. Leukocyte-related markers, such as CD68, macrophage matrix metalloprotease-9, CD177 and neutrophil elastase were often but not always detected in the niches. We suggest that SDF-1α is involved in homing of CXCR4+ GSLCs and leukocytes and that cathepsin K and osteopontin are involved in the migration of GSLCs out of the niches.
authors: Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands (VVVH, KJP, FG, WT, RJM, CJFVN)
authors: Vashendriya V V
authors: VV
authors: Hira
authors: Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands (VVVH, KJP, FG, WT, RJM, CJFVN)
authors: Kimberley J
authors: KJ
authors: Ploegmakers
authors: Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands (VVVH, KJP, FG, WT, RJM, CJFVN)
authors: Frederieke
authors: F
authors: Grevers
authors: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia (UV, TLT)
authors: Urška
authors: U
authors: Verbovšek
authors: Department of (Neuro)Pathology, Academic Medical Center and Swammerdam Institute for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands (CSR, EA)
authors: Carlos
authors: C
authors: Silvestre-Roig
authors: Department of (Neuro)Pathology, Academic Medical Center and Swammerdam Institute for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands (CSR, EA)
authors: Eleonora
authors: E
authors: Aronica
authors: Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands (VVVH, KJP, FG, WT, RJM, CJFVN)
authors: Wikky
authors: W
authors: Tigchelaar
authors: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia (UV, TLT)|Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia (TLT)
authors: Tamara Lah
authors: TL
authors: Turnšek
authors: Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands (VVVH, KJP, FG, WT, RJM, CJFVN)
authors: Remco J
authors: RJ
authors: Molenaar
authors: Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, The Netherlands (VVVH, KJP, FG, WT, RJM, CJFVN)
authors: Cornelis J F
authors: CJ
authors: Van Noorden
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001160:Arterioles / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D056657:Cathepsin K / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000098:blood supply / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells; D064231:Nestin / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D055153:Stem Cell Niche / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D054377:Chemokine CXCL12; D006023:Glycoproteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D056657:Cathepsin K
keywords: CXCR4; cathepsin K; glioma stem-like cells; leukocytes; migration; niches; osteopontin; stromal derived factor-1α