Nandhu et al. discovered that Fibulin-3, a protein secreted by glioma cells, acts as a paracrine activator of Notch signaling, motivating angiogenesis in high-grade glioma.364 Mechanistically, Fibulin-3 enhances the expression of DLL4 in an ADAM10/17-dependent manner, thereby activating DLL4-Notch signaling. Here, EFEMP1 is linked to central nervous system cancer.