Response-predictive gene expression profiling of glioma progenitor cells in vitro

PLoS One. 2014 Sep 30;9(9):e108632. doi: 10.1371/journal.pone.0108632. eCollection 2014.

Abstract

Background: High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.

Methods: In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a) to enrich specimens for brain tumor initiating cells and (b) to confront cells with a therapeutic agent before expression profiling.

Results: As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.

Conclusion: For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers, Pharmacological / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Indoles / pharmacology*
  • Microarray Analysis
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Pyrroles / pharmacology*
  • Signal Transduction
  • Sunitinib
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Biomarkers, Pharmacological
  • Indoles
  • Neoplasm Proteins
  • Pyrroles
  • Sunitinib

Grants and funding

The work was supported by an unrestricted grant of the Wilhelm Sander-Stiftung, Munich, Germany (http://www.wilhelm-sander-stiftung.de/cms/front_content.php), grant number 2009-803-1, and by BioSysNet, Germany (http://www.biosysnet.de). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.