A Role for Matrix Remodeling Proteins in Invasive and Malignant Meningiomas

Invasive and malignant meningiomas present a significant therapeutic challenge due to high recurrence rates and invasion into surrounding bone, brain, neural and soft tissues. Understanding the mechanism of invasion could help in designing novel therapeutic approaches to prevent the need for repeat surgery, decrease morbidity and improve patient survival. The aim of this study was to identify the differential gene and protein expression profile in bone-invasive and malignant versus non-invasive meningiomas, focusing on factors that regulate invasion and identifying molecular mechanism of invasion.

Samples from bone-invasive, non-invasive and malignant meningiomas were used for RNA microarray, quantitative real-time PCR or Western blot analyses. Malignant meningioma cell lines (F5) were used for in vitro functional assays.

RNA microarray data analysis identified over 300 differentially expressed genes in bone-invasive versus non-invasive meningiomas. Ingenuity pathway analysis showed cell movement and invasion pathway among the significantly enriched networks, with an increased expression of its molecules including ADAMTS4, MMP19 and MMP16. Real-time PCR and western blotting analyses identified only increased expression of MMP16 in malignant WHO grade II and III meningiomas. Knock down of MMP16 was associated with a reduction in MMP2 gelatinase activity and a decrease in invasion, migration, survival and proliferation of meningioma tumor cells in vitro.

Overall, our data supports a role for MMP16 in invasive phenotype of the meningioma tumors. Further studies are required to explore the potential value of targeting matrix metalloproteinases, including MMP16, in clinical settings.