Adenosine receptor mediates motility in human melanoma cells.
Cell motility is an essential component of tumor progression and metastasis. A number of factors, both autocrine and paracrine, have been found to influence cell motility. In the present study, adenosine and adenine nucleotides directly stimulated chemotaxis of A2058 melanoma cells in the absence of exogenous factors. Three adenosine receptor agonists stimulated motility in the melanoma cells and two adenosine receptor antagonists strongly inhibited the chemotactic response to both adenosine and AMP. The chemotactic stimulation by adenosine and AMP was pertussis toxin sensitive. Otherwise unresponsive Chinese hamster ovary cells which were transfected with the adenosine A1 receptor cDNA acquired the direct, pertussis toxin sensitive, chemotactic response to adenosine, and this response was inhibited by adenosine receptor antagonists. These findings demonstrate that adenosine and adenine nucleotides are capable of stimulating chemotaxis of tumor cells mediated through an adenosine receptor, probably of the A1 subtype. The possibility of antimetastatic therapies based on inhibition of adenosine receptor activity is raised.
Woodhouse
E C
EC
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. elisa@box-e.nih.gov
Amanatullah
D F
DF
Schetz
J A
JA
Liotta
L A
LA
Stracke
M L
ML
Clair
T
T
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002633:Chemotaxis; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism*; D037342:Pertussis Toxin; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C112774:1,3-dimethyl-8-cyclopentylxanthine; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D014970:Xanthines; C047235:N-(1-methyl-2-phenylethyl)adenosine; C048599:N(6)-cyclopentyladenosine; D000249:Adenosine Monophosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D037342:Pertussis Toxin; D000241:Adenosine