gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit den Benelux-Ländern und Bulgarien

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

24. - 27.05.2009, Münster

Growth mechanisms of CNS hemangioblastomas

Meeting Abstract

  • S. Gläsker - Abteilung Allgemeine Neurochirurgie, Universitätsklinikum Freiburg
  • A. Vortmeyer - Yale University Medical Center, New Haven, USA
  • B. Schatlo - National Institutes of Health, Surgical Neurology Branch, Bethesda, USA
  • R. Lonser - National Institutes of Health, Surgical Neurology Branch, Bethesda, USA
  • R. Pluta - National Institutes of Health, Surgical Neurology Branch, Bethesda, USA

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP08-02

DOI: 10.3205/09dgnc330, URN: urn:nbn:de:0183-09dgnc3301

Veröffentlicht: 20. Mai 2009

© 2009 Gläsker 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

Text

Objective: Patients with von Hippel-Lindau (VHL) disease develop multifocal CNS hemangioblastomas due to the inactivation of the VHL tumor suppressor gene. Recent studies indicate that VHL inactivation and subsequent up-regulation of hypoxia inducible factor (HIF) alone is insufficient to promote neoplastic proliferation in vivo and in vitro. Nitric oxide (NO) modifies the growth of various types of human neoplasia. Furthermore, NO synthases (NOS) are downstream targets of HIF.

Methods: We therefore examined the presence of NO in VHL disease-associated hemangioblastomas by determining nitrite levels using a newly developed, ferricyanide-based hemoglobin oxidation assay. In addition, we evaluated NOSes, and several NO-cGMP pathway-modulating enzymes in these tumors. The growth pattern of the tumors used for this study had been characterized in detail over a period of at least one year prior to surgery.

Results: Production of NO was confirmed by significantly elevated nitrite levels in hemangioblastoma compared to corresponding blood samples (n=7, p=0.018) with higher levels in faster growing tumors. Hemangioblastoma tumor cells expressed both inducible and endothelial NOS. Simultaneously, the tumor cells expressed enzymes inhibiting the activity of NOS (diamethylarginine dimethylamine hydrolase [DDAH2]; protein-arginine methyl transferase [PRMT]) and NO-dependent enzymes of the apoptotic pathway (soluble guanylyl cyclase [sGC]; phosphodiesterase [PDE V]). TUNEL assay in these tumors did not reveal prominent apoptosis.

Conclusions: The presence of NOS, NO, and the enzymes regulating the NO-cGMP pathway in hemangioblastoma tumor cells suggests that NO is involved in tumor growth and may contribute to the unusual saccadic growth of hemangioblastomas. Targeting NO metabolism may provide new diagnostic and therapeutic options for hemangioblastomas.