title: Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens.
abstract: Human brain tumors appear to have a hierarchical cellular organization suggestive of a stem cell foundation. In vitro expansion of the putative cancer stem cells as stable cell lines would provide a powerful model system to study their biology. Here, we demonstrate routine and efficient derivation of adherent cell lines from malignant glioma that display stem cell properties and initiate high-grade gliomas following xenotransplantation. Significantly, glioma neural stem (GNS) cell lines from different tumors exhibit divergent gene expression signatures and differentiation behavior that correlate with specific neural progenitor subtypes. The diversity of gliomas may, therefore, reflect distinct cancer stem cell phenotypes. The purity and stability of adherent GNS cell lines offer significant advantages compared to "sphere" cultures, enabling refined studies of cancer stem cell behavior. A proof-of-principle live cell imaging-based chemical screen (450 FDA-approved drugs) identifies both differential sensitivities of GNS cells and a common susceptibility to perturbation of serotonin signaling.
authors.affiliation: Wellcome Trust Centre for Stem Cell Research and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. steve.pollard@cscr.cam.ac.uk
authors.forename: Steven M
authors.initials: SM
authors.lastname: Pollard
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Ian D
authors.initials: ID
authors.lastname: Clarke
authors.forename: Davide
authors.initials: D
authors.lastname: Danovi
authors.forename: Stefan
authors.initials: S
authors.lastname: Stricker
authors.forename: Roslin
authors.initials: R
authors.lastname: Russell
authors.forename: Jane
authors.initials: J
authors.lastname: Bayani
authors.forename: Renee
authors.initials: R
authors.lastname: Head
authors.forename: Marco
authors.initials: M
authors.lastname: Lee
authors.forename: Mark
authors.initials: M
authors.lastname: Bernstein
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Dirks
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D046508:Culture Techniques; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D005910:Glioma / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012701:Serotonin / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D012701:Serotonin