gms | German Medical Science

67th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Korean Neurosurgical Society (KNS)

German Society of Neurosurgery (DGNC)

12 - 15 June 2016, Frankfurt am Main

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Human glioblastoma stem-like cells accumulate protoporphyrin IX when subjected to 5-aminolaevulinic acid, rendering them sensitive to photodynamic treatment

Meeting Abstract

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  • Thomas Beez - Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany
  • Adrian Schimanski - Institut für Transplantationsdiagnostik und Zelltherapeutika, Heinrich-Heine-Universität, Düsseldorf, Germany
  • Michael C. Sabel - Neurochirurgische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany
  • Katrin Lamszus - Neurochirurgische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Christian Ewelt - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Münster, Münster, Germany
  • Rüdiger V. Sorg - Institut für Transplantationsdiagnostik und Zelltherapeutika, Heinrich-Heine-Universität, Düsseldorf, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocMI.10.02

doi: 10.3205/16dgnc283, urn:nbn:de:0183-16dgnc2832

Published: June 8, 2016

© 2016 Beez 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: Glioblastoma (GBM) can be grown in vitro as neurospheres containing glioblastoma stem-like cells (GSC). GSC share numerous genetic and biological alterations with the original tumor and are suspected to be the driving force for disease recurrence. Thus, efficacy of emerging therapies such as 5-aminolaevulinic acid-mediated photodynamic therapy (5-ALA/PDT), may depend on targeting GSC. 5-ALA/PDT utilizes the selective accumulation of the photosensitizer protoporphyrin IX (PPIX) in GBM cells after application of 5-ALA. When exposed to laser light of 635 nm wavelength, PPIX initiates a photochemical reaction, resulting in the generation of reactive oxygen species, which kill the tumor cells. Whether GSC accumulate PPIX and are sensitive to 5 ALA/PDT is currently unknown.

Method: GSC were grown as neurospheres under serum-free conditions in the presence of basic fibroblast growth factor and epidermal growth factor. They were treated with graded doses of 5-ALA, and accumulation of PPIX was determined by flow cytometry. After exposure to laser light of 635 nm wavelength, viability of cells was studied using the WST-1 assay.

Results: When subjected to exogenous 5-ALA, a dose- and time-dependent accumulation of PPIX in GSC was observed, which varied between individual GSC preparations. Subsequent exposure to laser light substantially killed GSC, whereas treatment with 5-ALA or exposure to laser light only had no effect. LD50 values differed between GSC preparations, but were negatively correlated with PPIX accumulation in GSC.

Conclusions: We report for the first time that glioblastoma stem-like cells accumulate PPIX when subjected to 5-aminolaevulinic acid and are sensitive to 5-aminolaevulinc acid based photodynamic therapy.