ANGI-10. IMPLICATIONS OF EPITHELIAL MEMBRANE PROTEIN-2 (EMP2) IN THE PATHOGENESIS OF MENINGIOMAS

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Abstract INTRODUCTION VEGF-A is an important mediator of angiogenesis in meningiomas. However, targeting this protein with bevacizumab has offered only a modest improvement in survival, suggesting that there are other compensatory mechanisms involved, enabling vascularization despite ongoing treatment. Epithelial membrane protein 2 (EMP2), a cell surface protein, promotes angiogenic processes in gynecological cancers and brain tumors including gliomas and glioblastoma. However, little is known about its etiology and mechanism of action within meningiomas. OBJECTIVE We aimed to evaluate EMP2 expression in non-pathologic brain tissue, tumor specimens, and in meningioma cell lines. We also aimed to understand its mechanism within cells with regard to proliferation and invasion. METHODS Non-pathologic brain tissues from routine autopsies and tumor specimens from surgical resection were analyzed. Additionally, four meningioma cell lines were obtained (CH157, BEN-MEN1, SF1335 and IOMM-LEE) and changes in cellular proliferation and invasion were measured. Furthermore, EMP2 expression was modulated using lentiviral infection. A p-value < 0.05 was considered statistically significant. RESULTS EMP2 mRNA and protein expression were significantly higher in the meningioma specimens compared to non-pathologic meninges. Its expression also positively correlated with an angiomatous pattern and VEGF-A mRNA expression. In vitro, high EMP2 protein expression was noted in all cell lines, and quantification demonstrated highest expression in the malignant cell line, the IOMM-LEE. Viral vectors were subsequently utilized to create EMP2 overexpressing and knockdown IOMM-LEE models. Western analysis demonstrated a correlation between EMP2 overexpression and HIF1α, a key mediator of tumor growth and angiogenesis. CONCLUSION Our data from primary tumor samples and in vitro models implicate EMP2 in meningioma pathogenesis. This warrants further investigation by evaluating the effects of anti-EMP2 therapy on tumor growth and invasiveness in both in vitro andin vivo models.