gms | German Medical Science

69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

03.06. - 06.06.2018, Münster

Tyrosine kinase receptor AXL mediates chemo-resistance in glioblastoma

Meeting Abstract

  • Julia Onken - Charité - Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Lea Scherschinski - Charité - Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
  • Peter Vajkoczy - Charité - Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie. Münster, 03.-06.06.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. DocV264

doi: 10.3205/18dgnc282, urn:nbn:de:0183-18dgnc2823

Published: June 18, 2018

© 2018 Onken et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Tyrosine kinase receptor AXL (AXL) plays a role in tumor progression and therapy resistance in cancer. Targeted AXL inhibition is leading to decreased proliferation, migration and neo-vascularization of glioblastoma in vitro and in vivo. Previous studies show that AXL might play a role in chemo-resistance. With this study we want to investigate the role of AXL in therapy resistant glioma cell lines.

Methods: Human glioma cell lines U118MG and SF126 were exposed to increasing dosage of temozolomide (TMZ, 10, 50, 100, 150µM) over a period of 3-6 month to achieve chemo-resistance. Cell viability and chemo-sensitivity was measured with MTT assay. Polymerase chain reaction (qPCR), Western blot (WB) and Immunoprecipitation (IP) was performed to determine full-length AXL (FL-AXL), C-terminal AXL (CT-AXL) phosphorylation of FL-AXL and CT-AXL. Activation grade of multiple kinase receptors was detected with Proteome Profiler Human Phospho-Kinase Array.

Results: U118MG and SF126 showed increasing AXL mRNA and AXL protein expression under long-term TMZ treatment (10, 50, 100 and 150µM). Exposure of U118MG to therapeutic TMZ dosages (10 and 50 µM) resulted to an increase of AXL activation (P-AXL), whereas high TMZ dosages (100 and 150 µM) were reducing FL-AXL expression and increasing CT-AXL on protein level. AXL mRNA remained unchanged under 10, 50, 100 and 150 µM TMZ. Besides P-AXL, EGFR, PDGFR and ALK were up regulated under long-term TMZ exposure.

Conclusion: Long-term TMZ exposure is leading to chemo-resistance of glioma cells, resulting in an increasing of AXL expression and activation (P-AXL). In context of chemo-resistance AXL expression underlies mostly posttranslational modifications. Our results are indicating that AXL inhibition might be a suitable strategy to restore chemo-sensitivity in TMZ resistant glioma cells.