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

The thrombin receptor system acts as a highly potent growth factor system in human glioblastomas

Meeting Abstract

  • S. Kuhn - Klinik für Neurochirurgie, Universitätsklinikum Jena
  • L. Handel - Klinik für Neurochirurgie, Universitätsklinikum Jena
  • H. Kosmehl - Pathologie, Helios-Klinikum Erfurt
  • E. Haciyakupoglu - Klinik für Neurochirurgie, Universitätsklinikum Jena
  • U.K. Hanisch - Neuropathologie, Universitätsklinikum Göttingen
  • R. Kalff - Klinik für Neurochirurgie, Universitätsklinikum Jena

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. DocMI.05-09

DOI: 10.3205/09dgnc200, URN: urn:nbn:de:0183-09dgnc2008

Veröffentlicht: 20. Mai 2009

© 2009 Kuhn 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: Thromboembolism has a high incidence in glioma patients. We believe this to be an outward sign of an aggressive glioma caused by the action of the thrombin-receptor-system. This study shows that coagulation factors and their receptors are expressed in human glioblastomas, and that there is an association with the preoperative systemic coagulation and that we see effects on the glioma growth.

Methods: We included brain tumor material of 60 patients and 42 patients with glioblastomas from a total of 184 brain tumor patients. Primary antibodies against pro-thrombin, thrombin, factor X, and the receptors PAR type 1 through 4 were tested. Patient blood was tested perioperatively for the coagulation factor activity. Cellular changes triggered by thrombin were analysed. Receptor physiology was evaluated. Effect on glioma metabolism was measured by NO and WST-1. BrdU assays and total cell counts were performed.

Results: Prothrombin, thrombin, factor X and their receptors PAR1 to PAR4 are expressed in human gliomas. The higher the WHO grade, the stronger was the expression of the coagulation factors and the receptors. A striking feature of any glioma was the total overlay between the expression areas of positive coagulation factor and its corresponding receptors. Furthermore, in the glioblastoma group out of 184 brain tumor patients tested for the systemic coagulation factor activity, the factors II, VIII, IX, and XI were significantly more active than in the controls. Glioblastoma cells carry mRNA for the thrombin receptor and exhibit a more branched and migratory phenotype upon exposure to the coagulation factor thrombin. Stimulation of the cells with thrombin raises the intracellular calcium from extra- and intracellular components. Coagulation blockers inhibit this signal. The addition of thrombin and PAR agonists significantly increases tumor redox activity and massively enhances tumor DNA synthesis and proliferation. These effects are blocked by coagulation inhibitors.

Conclusions: Gliomas express coagulation factors and their receptors. The expression is correlated to the WHO grade. Patients with glioblastomas perioperatively show a significantly increased activity of the coagulation factors II, VIII, IX, and XI. Stimulation of coagulation receptors results in a raised level of metabolism and proliferation. In summary, one could imagine a growth support for the glioblastoma caused by increased systemic coagulation activity.