EDN2 and neoplasm: Hypoxic tumor cells around dying tumor cells in the TC can also produce various kinds of cytokines regulated by HIF, such as C–C chemokine ligand type 5 (CCL5), CXCL12, vascular endothelial growth factor A (VEGF-A), endothelin (ET)-1, ET-2 and semaphorin-3A (Sema3A).