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

Neurokinin type 1-receptor-based targeting of glioblastoma multiforme with toxin-labelled substance P

Meeting Abstract

  • D. Cordier - Department of Neurosurgery, University Hospital Basel, Switzerland; Pharmazentrum, University Basel, Switzerland
  • M. Sailer - Department of Neurosurgery, University Hospital Basel, Switzerland; Pharmazentrum, University Basel, Switzerland
  • A. Gerber - Pharmazentrum, University Basel, Switzerland
  • L. Mariani - Department of Neurosurgery, University Hospital Basel, Switzerland; Pharmazentrum, University Basel, Switzerland

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. DocP 084

DOI: 10.3205/11dgnc305, URN: urn:nbn:de:0183-11dgnc3050

Published: April 28, 2011

© 2011 Cordier et al.
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Outline

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Objective: Local recurrence of glioblastoma multiforme (GBM) after standard treatment, i.e. surgery and radiochemotherapy, occurs in more than 90% of cases. Sufficient local tumor control positively correlates to improved survival. Neurokinin type 1-receptors (NK1-R) are overexpressed in GBM. In previous clinical trials, NK1-R overexpression has successfully been exploited by intratumoral injection of radiolabelled substance P (SP). However, the therapeutic effect of radiolabelled SP was difficult to predict despite proven NK1-R expression. Furthermore, radiopharmaceuticals carry substantial disadvantages. The presented study aims at the development of a non-radioactive, SP-based local therapeutic system and at the elucidation of the underlying therapeutic mechanism.

Methods: In this experimental study we examined nine established human GBM cell lines quantifying the expression levels of NK1-R by qRT-PCR and Western Blot, thereby discriminating between the full-length NK1-R-variant and the truncated NK1-R variant. The cell lines were exposed to toxin-SP-conjugates. Saporin and cholera-toxin were used as toxins. Cell survival and proliferation were quantified in a standardized photometric assay. Furthermore, we examine the intracellular translocation of the conjugates and their action on physiological NK1-R signalling.

Results: NK1-R were expressed in all GBM cell lines with a more than 12-fold difference in expression levels. Choleratoxin-SP remained without effect on cell proliferation in all cell lines. Saporin-SP exhibited a cytoreductive effect on six cell lines, with an impressive specific effect in one cell line. The level of NK1-R expression did not correlate with the cytoreductive effect. Predominant expression of full-length NK1-R seems to be a prerequisite for a specific cytoreductive effect, cell lines with predominant expression of truncated NK1-R responded unspecifically to saporin-SP.

Conclusions: Toxin-SP-conjugates may be promising candidates for effective local GBM treatment. Further analysis of permissive or inhibitory factors besides the expressed NK1-R subtype on the action of the toxin-SP-compounds is ongoing.