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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

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Targeting EGF-receptor in malignant gliomas with double stranded RNA poly(I:C) and polyethylene glycol-linear polyethylenimine as a carrier molecule

Meeting Abstract

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  • V. Albrecht - Tumorbiologisches Labor, Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München
  • J. Thorsteinsdottir - Tumorbiologisches Labor, Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München
  • E. Wagner - Pharmaceutical Biotechnology, Center for System-based Drug Research, Department of Pharmacy, Klinikum der Universität München
  • J.C. Tonn - Tumorbiologisches Labor, Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München
  • M. Ogris - Pharmaceutical Biotechnology, Center for System-based Drug Research, Department of Pharmacy, Klinikum der Universität München
  • C. Schichor - Tumorbiologisches Labor, Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München

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.05.08

doi: 10.3205/11dgnc027, urn:nbn:de:0183-11dgnc0273

Published: April 28, 2011

© 2011 Albrecht et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Glioblastoma multiforme (GBM) is characterized by an over-expression of the wtEGF receptor (EGFR) and its variant vIII (deltaEGFR), which is important for proliferation, invasion and angiogenesis of glial tumor cells. Targeted cellular delivery of proapoptotic, immune stimulatory double-stranded RNA polyinosinic:polycytidylic acid (poly(I:C)) via this receptor can be of therapeutical importance and was aim of this study.

Methods: For this study, tissue samples from glioblastomas (n=4) and non-neoplastic brain (n=2) have been stained immunohistochemically for EGFR/deltaEGFR expression. Additionally, different malignant glioma cell lines (U87, U251, U373, U138, U87wtEGFR, U87deltaEGFR) as well as cell subpopulations (endothelial cells (gbECs), mesenchymal stem like cells (gbMSCs), CD133-positive cells) isolated from GBM specimen in early passages (p<5) have been analyzed via immunocytochemistry and flow cytometry. Virus sized particles (polyplexes) were formed with RNA and a nucleic acid carrier conjugate based on linear polyethylenimine (LPEI) and an EGF receptor targeting ligand. Cells were then exposed to poly(I:C) polyplexes, the respective control poly(I) polyplexes or no polyplex for up to 48h. Inhibition of proliferation was measured with the sulforhodamine-B (SRB) proliferation assay.

Results: As expected, over-expression of EGFR was found in all glioma samples, compared to non-neoplastic brain. All tumor cell lines displayed over-expression of EGFR, except EGFR-negative U138-cells. The primary cultures, derived from GBM showed strong positivity for EGFR, whereas other subpopulations (gbMSCs, CD133-positive cells) only showed weak positivity. Endothelial cells displayed no EGFR-staining at all. Incubation of the cell lines and isolated cells with poly(I:C) polyplexes resulted in effective suppression of proliferation, depending on the EGF-receptor expression.

Conclusions: Tumor cell proliferation was effectively inhibited by treatment with the dsRNA-containing polyplexes targeting EGFR in malignant glial tumor cells. These findings render this agent a promising new candidate for a potential tumor cell receptor targeted therapy in glioblastoma.