ADENOSINE RECEPTOR MEDIATES MOTILITY IN HUMAN-MELANOMA CELLS

Cell motility is an essential component of tumor progression and metas tasis. A number of factors, both autocrine and paracrine, have been fo und to influence cell motility. In the present study, adenosine and ad enine nucleotides directly stimulated chemotaxis of A2058 melanoma cel ls in the absence of exogenous factors. Three adenosine receptor agoni sts stimulated motility in the melanoma cells and two adenosine recept or antagonists strongly inhibited the chemotactic response to both ade nosine and AMP. The chemotactic stimulation by adenosine and AMP was p ertussis toxin sensitive. Otherwise unresponsive Chinese hamster ovary cells which were transfected with the adenosine A(1) receptor cDNA ac quired the direct, pertussis toxin sensitive, chemotactic response to adenosine, and this response was inhibited by adenosine receptor antag onists. These findings demonstrate that adenosine and adenine nucleoti des are capable of stimulating chemotaxis of tumor cells mediated thro ugh an adenosine receptor, probably of the A(1) subtype, The possibili ty of antimetastatic therapies based on inhibition of adenosine recept or activity is raised. (C) 1998 Academic Press.