title: CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles.
abstract: Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)-derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell-like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133(+) subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133(-) tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133(-) glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133(+) CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133(-) tumor cells with apparent stem cell-like properties but distinct molecular profiles and growth characteristics in vitro and in vivo.
authors.affiliation: Laboratory of Neurooncology, University of Regensburg, Regensburg, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Beier
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.forename: Martin
authors.initials: M
authors.lastname: Proescholdt
authors.forename: Annette
authors.initials: A
authors.lastname: Lohmeier
authors.forename: Jörg
authors.initials: J
authors.lastname: Wischhusen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Oefner
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
authors.forename: Alexander
authors.initials: A
authors.lastname: Brawanski
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Beier
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D010455:Peptides / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse