2026 Proffered Presentations
S152: ANTI-EMP2 THERAPY SUPPRESSES VEGF-MEDIATED ANGIOGENESIS AND CELL MIGRATION IN MALIGNANT MENINGIOMA
Mahlet A Mekonnen1; Anubav Chandla1; Brian Aguirre2; Khashayar Mozaffari1; Aryan Pandey1; Madhuri Wadehra2; Isaac Yang1; 1UCLA Department of Neurosurgery; 2UCLA Department of Pathology
Background: Recurrent and malignant meningiomas lack effective systemic therapies, highlighting the urgent need for novel molecular targets. Epithelial membrane protein-2 (EMP2), a tetraspan protein implicated in angiogenesis, has emerged as a driver of tumor progression through regulation of vascular endothelial growth factor-A (VEGF-A).
Methods: Using malignant meningioma cell lines (IOMM-LEE, CH157) from the UCLA Brain Tumor SPORE, we generated EMP2 vector control and knockdown models. Cells were analyzed by RNA sequencing, transcriptomic functional analysis, and migration assays. Anti-EMP2 monoclonal antibody (PG101) was tested against IgG controls to evaluate therapeutic efficacy.
Results: EMP2 was significantly overexpressed in meningiomas compared with normal meninges (p = 0.0013), confirmed by immunohistochemistry where H-scores were markedly higher in tumor specimens (p < 0.001). Public transcriptomic datasets revealed a strong positive correlation between EMP2 and VEGF-A expression. EMP2 knockdown downregulated VEGF expression (p < 0.001) and disrupted pathways linked to hypoxia response and mitotic regulation. Importantly, anti-EMP2 antibody treatment significantly reduced cell migration compared to IgG controls (p = 0.003), demonstrating direct therapeutic inhibition of tumor motility.
Conclusions: EMP2 is a molecular driver of angiogenesis and invasion in malignant meningioma, acting through VEGF-A regulation and hypoxia-associated signaling. Anti-EMP2 therapy significantly impairs cell migration, providing compelling preclinical evidence for EMP2 inhibition as a novel therapeutic strategy to reduce aggressiveness, progression, and recurrence in malignant meningiomas.
