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Maintenance of EGFR and EGFRvIII expressions in an in vivo and in vitro model of human glioblastoma multiforme
Authors:Stockhausen Marie-Thérése  Broholm Helle  Villingshøj Mette  Kirchhoff Maria  Gerdes Tommy  Kristoffersen Karina  Kosteljanetz Michael  Spang-Thomsen Mogens  Poulsen Hans Skovgaard
Affiliation:aDepartment of Radiation Biology, The Finsen Center, Copenhagen University Hospital, Copenhagen, Denmark;bDepartment of Neuropathology, The Diagnostic Center, Copenhagen University Hospital, Copenhagen, Denmark;cDepartment of Clinical Genetics, The Juliane Marie Center, Copenhagen University Hospital, Copenhagen, Denmark;dDepartment of Neurosurgery, The Neuro Center, Copenhagen University Hospital, Copenhagen, Denmark;eDepartment of Biomedicine, University of Copenhagen, Copenhagen, Denmark
Abstract:Glioblastoma multiforme (GBM) is the most common, and most aggressive primary brain tumor among adults. A vast majority of the tumors express high levels of the epidermal growth factor receptor (EGFR) as a consequence of gene amplification. Furthermore, gene amplification is often associated with mutation of EGFR, and the constitutive activated deletion variant EGFRvIII is the most common EGFR mutation found in GBM. Activated EGFR signaling, through overexpression and/or mutation, is involved in increased tumorigenic potential. As such, EGFR is an attractive target for GBM therapy. However, clinical studies with EGFR inhibitors have shown inconsistent results, and as such, further knowledge regarding the role of EGFR and EGFRvIII in GBM is needed. For this, an appropriate in vivo/in vitro tumor model is required. Here, we report the establishment of an experimental GBM model in which the expressions of EGFR and EGFRvIII are maintained both in xenograft tumors growing subcutaneously on mice and in cell cultures established in stem cell conditions. With this model it will be possible to further study the role of EGFR and EGFRvIII, and response to targeted therapy, in GBM.
Keywords:EGFR   EGFRvIII   Stem cells   Glioblastoma multiforme
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