Evaluation of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinse-2 (MMP-2) in sera of intracranial tumor patients

Growing evidence supports the hypothesis that extracellular proteinases, as the matrix metalloproteinases (MMPs), mediate many changes in the microenvironment that are essential both early in the tumorigenesis and after in tumor growth. Among all MMPs, gelatinase A and B (MMP-2 and MMP-9) are most often related to a malignant cellular phenotype and are considered potential biomarkers of malignant cancer. In our study, we evaluated gelatinolytic activities in the serum of patients with intracranial neoplasms, in order to verify whether MMP-2 and MMP-9 might be considered potential biomarkers, assessed with a noninvasive means of detection. By gelatin zymography we verified MMPs activity in a total of 65 patients: 25 meningiomas, 20 gliomas and 20 metastases. A total of 25 healthy volunteers were enrolled as controls. Zymography analysis showed 4 dominant gelatinolytic bands, respectively of 240, 130, 92 and 72 kDa. The most evident lytic activity was at 92 kDa (MMP-9), whereas MMP-2 (72 kDa) was less expressed. Our results showed that MMP-9 multimer (240 kDa) and MMP-9 (92 kDa) gelatinolytic activities were significantly enhanced in the serum of patients with neoplasms, compared with healthy controls (p<0.001). Moreover, we observed a significant difference of MMP-9 (both monomer and multimer) between metastases and meningiomas (p<0.05) and a not statistically significant trend towards a higher expression in gliomas if compared with meningiomas. No significant difference of MMP-2 serum levels was found among the three groups. Serologic data have been correlated with the immunohistochemical analysis performed on the paraffin- embedded tissue of the same patients. These results suggest that the less expensive evaluation of MMPs in serum might provide clinicians additional information on intracranial neoplasms.