gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

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Bortezomib sensitizes primary human esthesioneuroblastoma cells for TRAIL-induced apoptosis

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  • corresponding author presenting/speaker Ronald Koschny - Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland
  • Heidrun Holland - Biotechnologisch-Biomedizinisches Zentrum (BBZ), Leipzig
  • Jaromir Sykora - Universitätsklinikum, Heidelberg
  • Martin R. Sprick - Deutsches Krebsforschungszentrum (DKFZ), Heidelberg
  • Tobias L Haas - Deutsches Krebsforschungszentrum (DKFZ), Heidelberg
  • Tom M Ganten - Universitätsklinikum, Heidelberg
  • Wolfgang Krupp - Universitätsklinikum, Klinik f Neurochirurgie, Leipzig
  • Manfred Bauer - Universitätsklinikum, Inst f Neuropathologie, Leipzig
  • Peter Ahnert - Biotechnologisch-Biomedizinisches Zentrum (BBZ), Leipzig
  • Jürgen Meixensberger - Universitätsklinikum, Klinik f Neurochirurgie, Leipzig
  • Henning Walczak - Deutsches Krebsforschungszentrum (DKFZ), Heidelberg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO269

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk379.shtml

Veröffentlicht: 20. März 2006

© 2006 Koschny et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

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Purpose: Despite radical surgical therapy and post-operative irradiation of esthesio-neuroblastoma the survival rate remains highly unsatisfactory. Numerous chemotherapeutic drugs, including the new class of proteasome inhibitors, namely Bortezomib, have been shown to sensitize many tumor cell lines for the novel anticancer cytokine TRAIL. Data concerning primary tumor cells are rather rare. Here, we evaluated the potential and the mechanism of the treatment of primary esthesioneuroblastoma cells with Bortezomib in combination with TRAIL.

Methods: Primary tumor cells were isolated from surgical specimens of an esthesioneuoblastoma, characterized regarding the expression of components of the TRAIL pathway by Western blot analysis and immunohistochemistry, and treated with TRAIL, Bortezomib and a combination thereof. Cell viability and apoptosis induction were quantified. The influence of Bortezomib on the TRAIL pathway was analyzed at the level of TRAIL receptor expression and expression of intracellular regulators of TRAIL sensitivity. The composition of the TRAIL death inducing signaling complex (DISC) upon Bortezomib pretreatment was analyzed by immunoprecipitation in primary tumor cells.

Results: Although the original tumor material as well as isolated primary esthesio-neuroblastoma cells expressed all known components of the TRAIL pathway, tumor cells were completely resistant to TRAIL-induced apoptosis. However, subtoxic doses of Bortezomib could sensitize for TRAIL-induced apoptosis by upregulation of TRAIL death receptors at the cell surface, enhanced TRAIL DISC formation and upregulation of intracellular pro-apoptotic proteins like FADD, Bax, and Bak.

Conclusion: The combinatorial use of Bortezomib and TRAIL represents a promising new therapeutic option for the treatment of esthesioneuroblastoma cells.