Table 1.
Major angiogenic factors targeting endothelial cells in glioblastomas.
| Factor | Receptor | Mechanism |
|---|---|---|
| VEGF-A | VEGFR-1 and VEGFR-2 | Stimulates EC migration, proliferation, survival, nitric oxide production, and angiogenic response |
| ARL13B | VEGFR-2 | Binds the intracellular domain of VEGFR2 on ECs to promote VEGFA-VEGFR2 signaling |
| TGF-β | TβRII | Acts on both TCs and ECs to induce neovascularization and causes ECM remodeling using MMPs |
| FGF2 | FGFR | Stimulates EC VEGF production and proliferation |
| EGF | EGFR | Promotes EC migration and capillary tube formation |
| ETV2 | Conserved ETS motifs in the ZRS | Transdifferentiates GBM stem cells to an endothelial lineage |
| Pleiotrophin | ALK1 | Causes VEGF deposition at blood vessels, induces EC proliferation |
| PDFG-B | PDGF receptor β | Stimulates VEGF production in ECs |
| Ang-1 | EC-specific Tie receptors | Acts on ECs to stimulate angiogenesis and EC survival |
VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; ARL13B, ADP-ribosylation factor-like protein 13B; TGF-β, transforming growth factor-beta; TβRII, TGF-β type II receptor; FGF2, fibroblast growth factor 2; FGFR, fibroblast growth factor receptor; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ETV2, Ets variant 2; ALK1, activin receptor-like kinase 1; PDFG-B, platelet-derived growth factor B; Ang, angiopoietin; ZRS, zone of polarizing activity regulatory sequence.