pVHL-deficient tumor cells (hemangioblasts) in VHL-associated hemangioblastoma, unable to degrade HIF, produce downstream factors vascular endothelial growth factor (VEGF), platelet derived growth factor, erythropoietin, and endothelin secondary to pseudo-hypoxic cellular environment (A). HIF-dependent factor release stimulates hemangioblastoma tumor cells to differentiate into erythrocytes or endothelial cells, while also inducing angiogenesis within the existent tumor vascular network (B). De novo endothelial cells (V, vasculogenesis) can combine with migrating endothelial cells (A, angiogenesis), recruited during angiogenesis, during tumor blood vessel formation (C).