Introduction: Meningiomas are the most common primary intracranial neoplasm in adults. However, few treatment options are available for aggressive subtypes that recur despite surgery and radiation. Elucidation of critical mitogenic signaling pathways in meningioma oncogenesis may offer new therapeutic strategies. Osteoglycin (OGN) plays critical roles in both physiological and pathological conditions. We investigated the expression of OGN in human meningiomas, its function in meningioma cells and potential as a therapeutic target.
Methods: OGN mRNA expression in human meningiomas was obtained by RNA microarray and RNAscope. Stable overexpression of OGN in human malignant meningioma cell line was created to assay the impact of OGN on cell proliferation and colony formation, and mitogenic signaling cascades. Furthermore, the functional and signaling consequences of introducing an AKT inhibitor in OGN-overexpressing meningioma cells were assessed.
Results: OGN mRNA expression was dramatically increased in meningiomas compared to a range of other tumor types and normal brain. Furthermore, both OGN mRNA and protein were stably expressed in a malignant meningioma cell line, IOMM-Lee. Cell proliferation, cell cycle progression, and tumor cell colony formation were increased in OGN overexpressed meningioma cells as compared with meningioma cells transfected with control vectors. In addition, both NF2 mRNA and protein expression were attenuated in OGN-overexpressing cells. Conversely, mTOR pathway activation increased in OGN cells compared to control cells. Lastly, AKT inhibitor reduced OGN level in meningioma cells, and resulted in increased cell death and autophagy.
Conclusions: We identify OGN as a novel oncogene in meningioma proliferation. AKT inhibition reduces OGN protein levels in meningioma cells, with a concomitant increase in cell death, which provides a promising treatment option for clinical precise treatment of meningiomas with OGN overexpression.
Patient Care: OGN expression may serve as an addition biomarker to stratify the response of aggressive meningiomas to AKT inhibitors. This study lays a foundation for the identification of personalized treatment for meningiomas with OGN overexpression.
Learning Objectives: Identify a new oncogene to provide new treatment options for meningiomas