Adenosine receptors and human melanoma

Increased concentrations of extracellular adenosine are reached in ischemic or inflamed tissues but have also been detected inside tumoral masses. This latter finding may account for an important role of adenosine in the pathogenesis of tumors and its contradictory effects on cell survival and proliferation remain to be reconciled with the presence of specific adenosine receptor subtypes. This article reviews the pharmacological and biochemical characterization of adenosine receptors in the human malignant melanoma A375 cell line and the functional significance of their presence in a tumor cell type. We show that adenosine improves cell proliferation via A2A receptors while it arrests the cells at G1/G0 cell cycle phase through A3 stimulation. Furthermore, adenosine triggers a survival signal via A3 receptor stimulation while it simultaneously promotes cell death via A2A receptor activation, inducing a signaling pathway that involves protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs).