P2Y purinergic receptors regulate the growth of human melanomas

Abstract 

Adenosine 5′-triphosphate is known to function as a potent extracellular messenger producing its effects via a distinct family of cell surface receptors. Different receptor subtypes have been shown to modulate different cellular functions such as proliferation, differentiation and apoptosis. We investigated the functional expression and proliferative action of metabotropic P2Y receptors in human melanoma tissue and cells. Expression of functional P2Y₁, P2Y₂ and P2Y₆ receptor subtypes was established by reverse transcriptase polymerase chain reaction, immunohistochemistry and intracellular calcium measurements using a Fluorometric Imaging Plate Reader. Incubation of A375 melanoma cells with the P2Y₁ receptor-selective agonist 2-methylthioadenosine-5-diphosphate caused a decrease in cell number which was dose-dependent, whereas incubation with the P2Y₂ receptor agonist uridine triphosphate caused a dose-dependent increase in cell number. The action of extracellular nucleotides on P2Y receptors was shown to mediate the growth of melanomas and the P2Y₁ receptor is a putative target for melanoma therapy.

Keywords: Cancer, Melanoma, P2Y receptor, ATP