title: Cell line with endogenous EGFRvIII expression is a suitable model for research and drug development purposes.
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.
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.
authors.forename: Wojciech J
authors.initials: WJ
authors.lastname: Stec
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Rosiak
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Siejka
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Peciak
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Popeda
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Banaszczyk
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.|Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Roza
authors.initials: R
authors.lastname: Pawlowska
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Treda
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Hulas-Bigoszewska
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Sylwester
authors.initials: S
authors.lastname: Piaskowski
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Stoczynska-Fidelus
authors.affiliation: Research and Development Unit, Celther Polska Ltd., Lodz, Poland.|Department of Tumor Biology, Medical University of Lodz, Lodz, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Rieske
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D057166:High-Throughput Screening Assays; D006801:Humans; D009361:Neoplasm Invasiveness; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors
keywords: DK-MG; EGFR; EGFRvIII; glioblastoma