title: Proteomic analysis underlines the usefulness of both primary adherent and stem-like cell lines for studying proteins involved in human glioblastoma.
abstract: Primary cell lines derived as neurospheres, enriched in cancer stem cells, are currently the focus of interest in glioblastoma to test new drugs, because of their tumor initiating abilities and resistance to conventional therapies. However, not all glioblastoma samples are propagatable under neurosphere culture and not all neurosphere cell lines are tumorigenic. These cells therefore cannot recapitulate the heterogeneity of glioblastoma samples. We have conducted a proteomic analysis of primary glioblastoma cell lines derived either as adherent cells in the presence of serum (n=11) or as neurospheres (n=12). A total of 963 proteins were identified by nano-LC/Q-TOF MS: 342 proteins were found only in neurosphere lines and were mostly implicated in various metabolic and cellular processes, while 112 proteins were found only in adherent cells and mostly linked to cell adhesion. A protein signature of 10 proteins, 9 of them involved in a cell adhesion pathway, characterized adherent lines. Neurospheres were characterized by 73 proteins mostly linked to DNA metabolic processes associated to cell cycle and protein metabolism. In the Repository of Molecular Brain Neoplasia Data, expression of genes coding for several proteins related to adherent cells or neurospheres were of prognostic relevance for glioblastoma.
  
  
  CONCLUSIONS
  Primary cell lines enriched in cancer stem cells (CSC) have become popular models for testing new drugs for glioblastoma. In this proteomic study on an important number of cell lines obtained either as adherent cells in the presence of serum (a classic way to derive cell lines) or as neurospheres (enriched in CSC), we show that each type of cell line displays different GBM-specific features, highlighting that these two culture types are complementary tools for drug screening.
authors.affiliation: Department of Clinical Biology, Eugène Marquis Cancer Institute, Rennes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Collet
authors.affiliation: Department of Clinical Biology, Eugène Marquis Cancer Institute, Rennes, France; CNRS UMR 6290 Genetic and Development, University of Rennes 1, Rennes, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Avril
authors.affiliation: Biogenouest® Transcriptome Platform, University of Rennes 1, Rennes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Aubry
authors.affiliation: Department of Neurosurgery, University Hospital Rennes, France.
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Hamlat
authors.affiliation: Department of Neurosurgery, University Hospital Rennes, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Le Reste
authors.affiliation: Department of Pathology, University Hospital Rennes, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Chiforeanu
authors.affiliation: Department of Medical Oncology, Eugène Marquis Cancer Institute, Rennes, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Vauleon
authors.affiliation: CNRS UMR 6290 Genetic and Development, University of Rennes 1, Rennes, France; Medical Genomics Unit, Molecular Genetics and Genomics, University Hospital Rennes, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Mosser
authors.affiliation: Department of Clinical Biology, Eugène Marquis Cancer Institute, Rennes, France; CNRS UMR 6290 Genetic and Development, University of Rennes 1, Rennes, France. Electronic address: v.quillien@rennes.unicancer.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000737:chemistry*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005260:Female; D005909:Glioblastoma / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D020543:Proteome / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000737:chemistry*
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome
keywords: Cell lines; Glioblastoma; Proteomics; Stem-cells