Artikel
TF and TFPI mRNA expression is higher in malignant gliomas and causes higher TF and TFPI protein levels in glioblastoma multiforme compared to low grade gliomas
Die TF- und TFPI-mRNA Expression ist höher in Glioblastomen als in low-grade-Gliomen und führt zu einer höheren TF- und TFPI-Proteinkonzentration in malignen Gliomen
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
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Objective
Compared to benign brain tumors, plasma tissue factor pathway inhibitor (TFPI) level was found to be significantly higher in patients with malignant brain tumors. It was discussed, whether the increased plasma TFPI counteracts an enhanced activation of coagulation by high concentrations of tissue factor (TF), which could be released from tumor tissue into plasma via a disturbed blood brain barrier. Therefore the aim of this study was to determine the concentration of TF and TFPI and their mRNA expression in tumor samples from patients with glioblastomas (GBM) and low grade gliomas (LGG).
Methods
Tumor tissue was immediately prepared after removal of the tumor. For protein analysis, tissue was homogenized in PBS containing 1% Triton X-100 and frozen at -20°C. Commercially available ELISA kits were used to determine TF and TFPI. To determine protein concentration, the Bradford test was used. mRNA expression was analysed after semiquantitative RT-PCR using actin as internal standard and electrophoretic separation with ethidiumbromide staining of the PCR products. For quantification the phoretix TotalLab software, version 2.01 (biostep, GmbH) was used.
Results
TF and TFPI protein concentrations were higher in GBM (n=7) compared to LGG (n=6). Although not significant for TF (182.9 ± 78.6 vs. 109.5 ± 100ng · mg-1), TFPI was significantly higher in GBM (0.67 ± 0.12 ng · mg-1) than in LGG (0.36 ± 0.16 ng · mg-1; p<0.05; t-test). Similar results were found for mRNA levels of TF and TFPI. Expression of TF mRNA was 0.96 ± 0.47 in GBM and 0.53 ± 0.25 (p=0.08) in LGG. TFPI mRNA was significantly higher in GBM (n=13) compared to LGG (n=5) [1.6 ± 0.9 vs. 0.43 ± 0.3; p<0.05 t-test).
Conclusions
A similar expression pattern of TF and TFPI – high protein concentration and mRNA level in GBM and lower in LGG - emphasises the tight control of TF-initiated coagulation activation by TFPI. The occurrence of thromboembolic events may be due to an imbalance in TF and TFPI level and may be the cause of increased malignancy-related systemic coagulation activation.