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

The coagulation factor Xa is a new target in anti-glioblastoma therapy

Meeting Abstract

  • S. Kuhn - Neurochirurgische Klinik, Klinikum der Friedrich-Schiller-Universität, Jena, Deutschland
  • L. Handel - Neurochirurgische Klinik, Klinikum der Friedrich-Schiller-Universität, Jena, Deutschland
  • L. Liebmann - Neurochirurgische Klinik, Klinikum der Friedrich-Schiller-Universität, Jena, Deutschland
  • S. Frank - Neurochirurgische Klinik, Klinikum der Friedrich-Schiller-Universität, Jena, Deutschland
  • R. Kalff - Neurochirurgische Klinik, Klinikum der Friedrich-Schiller-Universität, Jena, Deutschland

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 087

DOI: 10.3205/11dgnc308, URN: urn:nbn:de:0183-11dgnc3080

Published: April 28, 2011

© 2011 Kuhn 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

Text

Objective: Patients with glioblastomas often suffer from thrombembolic complications that complicate the course of disease and reduce the patient’s quality of life or shorten the survival time in severe cases.

Methods: Patients with glioblastomas (n=35) were included into a prospective case-controlled study and correlated to control patients (n=35) to investigate the activity of the coagulation factors II, V, VII, VIII, IX, X, XI, XII, and XIII. Tumor samples of human glioblastomas (n=50), control tissues (n=40) and experimental gliomas of nude rats (n=5) and syngenic rats (n=20) were studied for their expression of the coagulation factor X. Proliferation tests and metabolism tests were performed with activation of human glioblastoma cells by factor X. Blockade of factor X effects was investigated by use of PPACK, antithrombin III, and low-molecular weight heparins.

Results: Glioblastoma patients displayed a pathologically increased activity of the coagulation factor X. Tissue of human glioblastomas massively expressed factor X, whereas control tissue was almost factor X negative. Human glioblastomas of nude rats also strongly expressed the coagulation factor X; and the experimental syngenic rat gliomas displayed an intensive staining pattern for factor X, too. The stimulation of human glioblastoma cells with the coagulation factor X resulted into a significantly enhanced cellular metabolism and a significantly increased DNA synthesis and cellular proliferation. The inhibition of factor X action was possible by PPACK, human antithrombin III, and all low-molecular weight heparins that lowered the cellular DNA synthesis, proliferation, and metabolism down to approximately 30%.

Conclusions: This study shows for the first time that the coagulation factor X in massively expressed in human glioblastomas and experimental gliomas, that the action of factor X promotes the malignant behaviour of tumor cells and that its inhibition results in a clear reduction of tumor cell proliferation and metabolism.