TNF and neoplasm: Activator and inhibitor proteins in addition to chemical signals released from tumor cells into the surrounding tumor stroma [480,481] include transcription factors (such as hypoxia-inducible factor 1-alpha (HIF-1α)), growth factors (such as VEGF, epidermal growth factor, platelet-derived growth factor), cytokines (such as TNF, IL-8), and proteases (such as cathepsin and metalloproteinases) [479,482].