Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens

Steven M Pollard, Koichi Yoshikawa, Ian D Clarke, Davide Danovi, Stefan Stricker, Roslin Russell, Jane Bayani, Renee Head, Marco Lee, Mark Bernstein, Jeremy A Squire, Austin Smith, Peter Dirks

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)568-80
Number of pages13
JournalCell Stem Cell
Volume4
Issue number6
DOIs
Publication statusPublished - 5 Jun 2009

Keywords

  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Culture Techniques
  • Drug Screening Assays, Antitumor
  • Gene Expression Profiling
  • Glioma
  • Humans
  • Mice
  • Mice, SCID
  • Neoplastic Stem Cells
  • Serotonin
  • Transplantation, Heterologous

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