Identifying RNA and Protein Expression Profile of Bone Invading and Non-Invading Meningiomas

Keywords: meningioma, gene, malignant meningioma, neuropathology, skull

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     Meningiomas are benign primary brain tumors however a subset causes hyperostosis and invasion of adjacent neural and soft tissues. Skull base bone-invading meningiomas represent a significant clinical challenge since complete surgical resection is often impossible resulting in higher recurrence rates and repeat surgery.
     This study aims to identify differential gene and protein expression profile of bone-invading and non-invading meningiomas.
     Archived specimens of 75 patients with bone invading meningiomas were selected.
     RNA and Tissue Microarray were performed on the samples. Array data was verified using real-time PCR. Meningioma cell lines were used for in-vitro and in-vivo functional studies. Matrigel invasion assay, immunostaining and western blotting used to characterize the behavior of these cells in vitro. Intracranial meningioma tumors were generated and small animal MRI was used to study tumor growth pattern and behavior.
     RNA microarray data identified 222 differentially expressed genes of which the overexpression of MMP16 and 19 were selected as novel matrix remodeling proteins involved in bone invasion. Meningioma cell lines with high invasive capacity showed increased RNA and protein levels of MMP16 and MMP19. siRNA inhibition of MMP16 demonstrated diminished proliferation and invasion in-vitro and in-vivo. The downstream signaling pathway form MMP16 was identfiied as MAPK and AKT. In vivo studies using xenograft meningioma tumor models showed the tumor growth and invasion to the underlying bone tissue and confirmed in vitro data.
     This is a retrospective study.
     We identify novel pathways that play an improtant contributary role to bone invasion in meningiomas.
     These results provide the basis of future studies to explore potential for targetting MMP16&19 in meningiomas.


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