title: A comparative study of the structural organization of spheres derived from the adult human subventricular zone and glioblastoma biopsies.
abstract: Sphere forming assays have been useful to enrich for stem like cells in a range of tumors. The robustness of this system contrasts the difficulties in defining a stem cell population based on cell surface markers. We have undertaken a study to describe the cellular and organizational composition of tumorspheres, directly comparing these to neurospheres derived from the adult human subventricular zone (SVZ). Primary cell cultures from brain tumors were found to contain variable fractions of cells positive for tumor stem cell markers (CD133 (2-93%)/SSEA1 (3-15%)/CXCR4 (1-72%)). All cultures produced tumors upon xenografting. Tumorspheres contained a heterogeneous population of cells, but were structurally organized with stem cell markers present at the core of spheres, with markers of more mature glial progenitors and astrocytes at more peripheral location. Ultrastructural studies showed that tumorspheres contained a higher fraction of electron dense cells in the core than the periphery (36% and 19%, respectively). Neurospheres also contained a heterogeneous cell population, but did not have an organization similar to tumorspheres. Although tumorspheres clearly display irregular and neoplastic cells, they establish an organized structure with an outward gradient of differentiation. We suggest that this organization is central in maintaining the tumor stem cell pool.
authors.affiliation: Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, Oslo University Hospital, Oslo, Norway. e.o.vik-mo@medisin.uio.no
authors.forename: Einar Osland
authors.initials: EO
authors.lastname: Vik-Mo
authors.forename: Cecilie
authors.initials: C
authors.lastname: Sandberg
authors.forename: Mrinal
authors.initials: M
authors.lastname: Joel
authors.forename: Biljana
authors.initials: B
authors.lastname: Stangeland
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
authors.forename: Morten Carstens
authors.initials: MC
authors.lastname: Moe
authors.forename: Wayne
authors.initials: W
authors.lastname: Murrell
authors.forename: Iver Arne
authors.initials: IA
authors.lastname: Langmoen
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002552:Cerebral Ventricles / Q000166:cytology*; D005909:Glioblastoma / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000502:physiology; D051381:Rats; D018874:Spheroids, Cellular / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor