Enzymatic activity of extracellular circulating proteasome in the CSF of patients with malignant Intrinsic and metastatic brain tumors: proof of concept.

Abstract

Malignant intrinsic brain tumors are a hazardous disease with limited life expectancy despite intensive research in new targeted treatment options. Lately, proteasome inhibitors have been identified as potent agents causing death in glioma cell lines. It is the aim of the present study to identify proteasomal activity in the CSF of patients suffering from malignant brain tumors. A total of 24 patients with histological confirmed brain tumors (12 malignant gliomas, 12 metastases) were included and CSF probes preoperatively analyzed for concentration and enzymatic activity of free circulating proteasome. Tumor volumina were assessed using the preoperative MRI and correlated with the CSF findings. Statistical analyses were performed using SPSS (18.0.3; SPSS Inc., Chicago, IL, USA). Extracellular proteasomes were found in all CSF samples showing enzymatic activity. Proteasome concentrations (28 ng/mL and 23 ng/mL, resp.) were elevated compared to a historical control group. Proteasomal enzymatic chymotrypsin-like activity was significantly raised in patients with gliomas (mean 31 fkat/ mL) compared to controls (P<0.049), whereas the enzymatic activity was not significantly elevated in metastases (P=0.109). In gliomas, neither concentration nor enzymatic activity correlated with the preoperative assessed tumor volume. This pilot study clearly showed that the proteasomal activity in the CSF is significantly elevated in patients with intrinsic brain tumors. Further studies need to identify the proteasomal concentration and enzymatic activity as a potential biomarker for the effectiveness of any treatment and for the early diagnosis of a possible recurrence of the disease.