gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

The neural cell adhesion molecule L1CAM confers chemoresistance to human glioblastoma progenitor cells

Meeting Abstract

  • S. Schmelz - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • S. Sebens - Institut für Experimentelle Medizin c/o Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein
  • K. Hattermann - Institut für Anatomie, Christian-Albrechts-Universität Kiel, Kiel
  • R. Mentlein - Institut für Anatomie, Christian-Albrechts-Universität Kiel, Kiel
  • M. Mehdorn - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • J. Held-Feindt - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMO.05.03

DOI: 10.3205/11dgnc022, URN: urn:nbn:de:0183-11dgnc0227

Published: April 28, 2011

© 2011 Schmelz et al.
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Outline

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Objective: Glioblastomas are highly malignant brain tumors marked by poor prognosis and unsatisfactory response to treatments such as radio- and chemotherapy. The neural cell adhesion molecule L1CAM is expressed in various types of cancers including glioblastoma and has been demonstrated to facilitate metastasis and progression. Our current study introduces a potential role for L1CAM in chemoresistance and glioblastoma stem cell development.

Results: We demonstrated by qRT-PCR and FACS, that L1CAM is expressed in glioblastomas and – as shown for T98G and 27/07 glioblastoma cells – can be induced by TGF-ß1 (qRT-PCR, Western Blot). Transfection with L1CAM (efficiency proven by qRT-PCR and Western Blot) of both human primary and regular glioblastoma cell lines, as well as glioblastoma progenitor spheroids yielded in higher chemoresistance after Temozolomide treatment - assessed via caspase-3/-7-assay. In addition, as discovered in scratch-assays, L1CAM enhanced migration of the named cell types. Vice versa, transfection with L1CAM siRNA clearly diminished chemoresistance and migration. Interestingly, we detected by qRT-PCR that during differentiation of glioblastoma progenitor spheroids, L1CAM as well as TGF-ß1 expression increases considerably.

Conclusions: L1CAM expression in several glioblastoma cell lines is inducible by TGF-ß1, a common and highly expressed cytokine in these highly malignant brain tumors. L1CAM enhances migration and chemoresistance in glioblastoma cell lines, primary cultures and glioblastoma progenitor cells. Therefore, L1CAM could play a role in glioblastomas’ bad response to chemotherapy.