Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma

Jonathon J. Parker, Kalen R. Dionne, Rada Massarwa, Marci Klaassen, Nicholas K. Foreman, Lee Niswander, Peter Canoll, B. K. Kleinschmidt-Demasters, Allen Waziri

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

BackgroundTissue invasion is a hallmark of most human cancers and remains a major source of treatment failure in patients with glioblastoma (GBM). Although EGFR amplification has been previously associated with more invasive tumor behavior, existing experimental models have not supported quantitative evaluation of interpatient differences in tumor cell migration or testing of patient-specific responses to therapies targeting invasion. To explore these questions, we optimized an ex vivo organotypic slice culture system allowing for labeling and tracking of tumor cells in human GBM slice cultures.MethodsWith use of time-lapse confocal microscopy of retrovirally labeled tumor cells in slices, baseline differences in migration speed and efficiency were determined and correlated with EGFR amplification in a cohort of patients with GBM. Slices were treated with gefitinib to evaluate anti-invasive effects associated with targeting EGFR.ResultsMigration analysis identified significant patient-to-patient variation at baseline. EGFR amplification was correlated with increased migration speed and efficiency compared with nonamplified tumors. Critically, gefitinib resulted in a selective and significant reduction of tumor cell migration in EGFR-amplified tumors.ConclusionsThese data provide the first identification of patient-to-patient variation in tumor cell migration in living human tumor tissue. We found that EGFR-amplified GBM are inherently more efficient in their migration and can be effectively targeted by gefitinib treatment. These data suggest that stratified clinical trails are needed to evaluate gefitinib as an anti-invasive adjuvant for patients with EGFR-amplified GBM. In addition, these results provide proof of principle that primary slice cultures may be useful for patient-specific screening of agents designed to inhibit tumor invasion.

Original languageEnglish
Pages (from-to)1048-1057
Number of pages10
JournalNeuro-oncology
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Keywords

  • EGFR
  • gefitinib
  • glioblastoma
  • invasion
  • migration
  • personalized therapy
  • slice culture

Fingerprint Dive into the research topics of 'Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma'. Together they form a unique fingerprint.

  • Cite this

    Parker, J. J., Dionne, K. R., Massarwa, R., Klaassen, M., Foreman, N. K., Niswander, L., Canoll, P., Kleinschmidt-Demasters, B. K., & Waziri, A. (2013). Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma. Neuro-oncology, 15(8), 1048-1057. https://doi.org/10.1093/neuonc/not053