Cell line with endogenous EGFR(vIII) expression is a suitable model for research and drug development purposes

Glioblastoma is the most common and malignant brain tumor, characterized by high cellular heterogeneity. About 50% of glioblastomas are positive for EGFR amplification, half of which express accompanying EGFR mutation, encoding truncated and constitutively active receptor termed EGFR(vIII). Currently, no cell models suitable for development of EGFR(vIII)-targeting drugs exist, while the available ones lack the intratumoral heterogeneity or extrachromosomal nature of EGFR(vIII). The reports regarding the biology of EGFR(vIII) expressed in the stable cell lines are often contradictory in observations and conclusions. In the present study, we use DK-MG cell line carrying endogenous non-modified EGFR(vIII) amplicons and derive a sub-line that is near depleted of amplicons, whilst remaining identical on the chromosomal level. By direct comparison of the two lines, we demonstrate positive effects of EGFR(vIII) on cell invasiveness and populational growth as a result of elevated cell survival but not proliferation rate. Investigation of the PI3K/Akt indicated no differences between the lines, whilst NFκB pathway was over-active in the line strongly expressing EGFR(vIII), finding further supported by the effects of NFκB pathway specific inhibitors. Taken together, these results confirm the important role of EGFR(vIII) in intrinsic and extrinsic regulation of tumor behavior. Moreover, the proposed models are stable, making them suitable for research purposes as well as drug development process utilizing high throughput approach.