Oncotarget

Research Papers:

Cell line with endogenous EGFRvIII expression is a suitable model for research and drug development purposes

Wojciech J. Stec _, Kamila Rosiak, Paulina Siejka, Joanna Peciak, Marta Popeda, Mateusz Banaszczyk, Roza Pawlowska, Cezary Treda, Krystyna Hulas-Bigoszewska, Sylwester Piaskowski, Ewelina Stoczynska-Fidelus and Piotr Rieske

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Oncotarget. 2016; 7:31907-31925. https://doi.org/10.18632/oncotarget.8201

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Abstract

Wojciech J. Stec1, Kamila Rosiak1,2, Paulina Siejka1,2, Joanna Peciak1,2, Marta Popeda1, Mateusz Banaszczyk1, Roza Pawlowska1,3, Cezary Treda1, Krystyna Hulas-Bigoszewska1, Sylwester Piaskowski1,2, Ewelina Stoczynska-Fidelus1,2 and Piotr Rieske1,2

1 Research and Development Unit, Celther Polska Ltd., Lodz, Poland

2 Department of Tumor Biology, Medical University of Lodz, Lodz, Poland

3 Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland

Correspondence to:

Wojciech J. Stec, email:

Keywords: EGFR, EGFRvIII, DK-MG, glioblastoma

Received: August 28, 2015 Accepted: March 10, 2016 Published: March 19, 2016

Abstract

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 EGFRvIII. Currently, no cell models suitable for development of EGFRvIII-targeting drugs exist, while the available ones lack the intratumoral heterogeneity or extrachromosomal nature of EGFRvIII.The reports regarding the biology of EGFRvIII 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 EGFRvIII 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 EGFRvIII 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 EGFRvIII, finding further supported by the effects of NFκB pathway specific inhibitors. Taken together, these results confirm the important role of EGFRvIII 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.


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