title: Arrested neural and advanced mesenchymal differentiation of glioblastoma cells-comparative study with neural progenitors.
abstract: BACKGROUND
  Although features of variable differentiation in glioblastoma cell cultures have been reported, a comparative analysis of differentiation properties of normal neural GFAP positive progenitors, and those shown by glioblastoma cells, has not been performed.
  
  
  METHODS
  Following methods were used to compare glioblastoma cells and GFAP+NNP (NHA): exposure to neural differentiation medium, exposure to adipogenic and osteogenic medium, western blot analysis, immunocytochemistry, single cell assay, BrdU incorporation assay. To characterize glioblastoma cells EGFR amplification analysis, LOH/MSI analysis, and P53 nucleotide sequence analysis were performed.
  
  
  RESULTS
  In vitro differentiation of cancer cells derived from eight glioblastomas was compared with GFAP-positive normal neural progenitors (GFAP+NNP). Prior to exposure to differentiation medium, both types of cells showed similar multilineage phenotype (CD44+/MAP2+/GFAP+/Vimentin+/Beta III-tubulin+/Fibronectin+) and were positive for SOX-2 and Nestin. In contrast to GFAP+NNP, an efficient differentiation arrest was observed in all cell lines isolated from glioblastomas. Nevertheless, a subpopulation of cells isolated from four glioblastomas differentiated after serum-starvation with varying efficiency into derivatives indistinguishable from the neural derivatives of GFAP+NNP. Moreover, the cells derived from a majority of glioblastomas (7 out of 8), as well as GFAP+NNP, showed features of mesenchymal differentiation when exposed to medium with serum.
  
  
  CONCLUSIONS
  Our results showed that stable co-expression of multilineage markers by glioblastoma cells resulted from differentiation arrest. According to our data up to 95% of glioblastoma cells can present in vitro multilineage phenotype. The mesenchymal differentiation of glioblastoma cells is advanced and similar to mesenchymal differentiation of normal neural progenitors GFAP+NNP.
authors.affiliation: Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland. piotrrieske@yahoo.com
authors.forename: Piotr
authors.initials: P
authors.lastname: Rieske
authors.forename: Ewa
authors.initials: E
authors.lastname: Golanska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zakrzewska
authors.forename: Sylwester
authors.initials: S
authors.lastname: Piaskowski
authors.forename: Krystyna
authors.initials: K
authors.lastname: Hulas-Bigoszewska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wolańczyk
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Szybka
authors.forename: Monika
authors.initials: M
authors.lastname: Witusik-Perkowska
authors.forename: Dariusz J
authors.initials: DJ
authors.lastname: Jaskolski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zakrzewski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Barbara
authors.initials: B
authors.lastname: Krynska
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Liberski
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D002449:Cell Aggregation / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002531:Cerebellum / Q000166:cytology; D066246:ErbB Receptors / Q000235:genetics; D016158:Genes, p53; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D019656:Loss of Heterozygosity; D008648:Mesoderm / Q000473:pathology; D053842:Microsatellite Instability; D009474:Neurons / Q000166:cytology* / Q000473:pathology; D010455:Peptides; D013234:Stem Cells / Q000166:cytology*; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; D066246:ErbB Receptors