Figure 2.

Tumor neovascularization in glioblastomas. In the setting of a tumor, stresses such as hypoxia prompt the release of signaling proteins, such as VEGF, ARL13B, TGF-β, FGF, and EGF. These proteins interact with receptors, such as VEGFR-2, on the endothelial cell membrane. This interaction prompts several downstream effects, including degradation of the basement membrane and ECM, fibroblast displacement, and endothelial cell invasion of the stroma. Over time, MMPs and other proteins remodel the ECM, and endothelial tip cells migrate to the end of budding vessels. Guided by VEGF gradients, these tip cells aid in the formation of a new basement membrane and capillary with the incorporation of endothelial cells, smooth muscle cells, and pericytes. Created with BioRender.com. ARL13B, ADP-ribosylation factor-like GTPase 13B; ECM, extracellular matrix; EGF, epidermal growth factor; FGF, fibroblast growth factor; MMP, matrix metallopeptidase; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor; VEGFR-2, vascular endothelial growth factor receptor-2.