Figure 3.

Role of β-adrenergic modulatory mechanisms in tumor development and progression. Release of catecholamines in the tumor tissue associated with activation of sympathoadrenal system, stimulates β-adrenergic receptors on melanoma and tumor microenvironment cells. In tumor cells it further induces an increase of cAMP formation which, in its turn, activates multiple intracellular signaling pathways, such as GATA1, CREB and ATF, initiating protumorigenic mechanisms. Adrenergic stimulation of tumor infiltrating immune cells (TIICs) increases the production of proinflammatory cytokines and matrix metalloproteinases (MMPs), also favoring tumor growth, invasion and metastasis.