Different forms of sera gelatinases in human intracranial neoplasias

Mounting evidence supports the view that extracellular proteinases, such as the matrix metalloproteinases, mediate many of the changes in the microenvironment either in early steps of tumor evolution or in late steps of tumor growth. Among all MMPs members, gelatinase A and B (MMP-2 and MMP-9) are most often linked to malignant phenotype of tumor cells and are considered potential biomarkers of malignant cancer. By zymography we evaluated gelatinolytic activities in a total of 65 patients with intracranial neoplasms. Of these 25 had meningioma, 20 glioma, and 20 intracranial metastasis. A total of 25 normal healthy volunteers with no concomitant illness were used as controls. Zymography analysis showed 4 dominant gelatinolytic bands of 240, 130, 92 and 72 kDa. The most abundant lytic activity is at 92 kDa (MMP-9), whereas MMP-2 (72 kDa) is present in lesser quantities. The degree of gelatin digestion was quantified using an image software. The molecular weight, volume and background of each band were determined and the relative amounts of the different forms of gelatinases were expressed as the integrated density x 10-3 of all the pixels above the background of each band. Our data showed that both MMP-9 multimer (240 kDa) and monomer (92 kDa) gelatinolytic activities were significantly enhanced in the sera from patients compared with healthy controls (p<0.001). Moreover, MMP-9 multimer and monomer were significantly higher in sera from metastasis group than meningioma individuals (p<0.05), and a not statistically significant trend towards a higher activity in gliomas compared with meningiomas. Finally, no significant difference of MMP-2 (72 kDa) levels was found in tumor patients compared with healthy controls. These results suggest that the inexpensive measurement of MMPs in serum might provide clinicians additional objective information on intracranial neoplasms.