gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

The role of RTK inhibitor targeting axl in glioma cell lines

Meeting Abstract

  • Julia Sophie Onken - Abteilung für Neurochirurgie, Campus Virchow Klinik der Charité, Berlin
  • Irina Kremenetskaia - Abteilung für Neurochirurgie, Campus Virchow Klinik der Charité, Berlin
  • Melina Nieminen-Kelhä - Abteilung für Neurochirurgie, Campus Virchow Klinik der Charité, Berlin
  • Robert Torka - Max-Planck-Institut für Biochemie, Martinsried
  • Axel Ullrich - Max-Planck-Institut für Biochemie, Martinsried
  • Peter Vajkoczy - Abteilung für Neurochirurgie, Campus Virchow Klinik der Charité, Berlin

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocMI.13.01

doi: 10.3205/13dgnc383, urn:nbn:de:0183-13dgnc3839

Published: May 21, 2013

© 2013 Onken et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: As previously reported the role of Receptor tyrosine kinase (RTK) in brain tumor growth become more important. Axl has been revealed as an important RTK, which mediates tumor growth and proliferation. Axl/gas6 overexpression has been found in a multitude of human cancers including glioblastoma, colon, breast, prostate, thyroid, lung cancer and melanoma. Axl mediates tumor migration and invasion besides its known involvement in proliferation and cell transformation. These observations lead to the development of specific Axl inhibitors: BMS, LDC and MPCD. Their functionality we now tested in glioma cell migration assays in vitro and in vivo.

Method: Cell lines SF126 and GL261 were taken in culture. In Boyden chamber assay the migratory ability under treatment with different compounds was investigated. The experiments were run with 50,000 cells per chamber. Inserts were coated with fibronectin (10µg/ml in cold PBS). Observation period varied between 3-12 hours. Compounds were tested in three different concentrations (12.5µM, 6.25µM and 3.125µM). For spheroid migration assay in brain slice cultures 3-7 day old mouse pups were used, brain hemispheres were placed on the tissue chopper and sectioned in 300µm slices coronary. Prelabeled spheroids with a diameter of 300µm were placed in the area between striatum and corpus callosum, migration was monitored on day 0, 2, 4, and 6 under microscope.

Results: Compounds were used with a dilution of 1:800. We saw a highly significant decrease of migration rate in SF126 treated with compound 2 and 3 (pcpd2=0.005, pcpd3=0.0008). After a migration period of 3-4 hours there was no significant decrease seen under treatment with compound 1 (pcpd1=0.02). Similar results were obtained with cell line GL261. There was a significant decrease of migration rate under treatment with compound 2 and 3 (pcpd2=0.02, pcpd3=0.005), whereas we saw a slight increase of migration rate under treatment with compound 1 (pcpd1=0.1).

Conclusions: Compound 2 and 3 show a strong impact on migration rate in both cell lines, whereas compound 1 seems to have no effect on the migration rate in SF162 and GL261 in vitro. In a pilot study we will next stereotactically implant brain tumor cells of SF162 in CD1NuNu mice and GL261 in black six mice. Compounds will be administered via subcutaneous, osmotic pumps. Tumor growth will be monitored in MRI. Further experiments will include skinfold chamber and cranial window.