Artikel
The coagulation factor Xa is a new target in anti-glioblastoma therapy
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Veröffentlicht: | 28. April 2011 |
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Gliederung
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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.