ADENOSINE MODULATES CELL-PROLIFERATION IN HUMAN COLONIC-CARCINOMA - II - DIFFERENTIAL BEHAVIOR OF HT29, DLD-1, CACO-2 AND SW403 CELL-LINES

In a previous study, we provided evidence that extracellular adenosine modulates growth of the poorly differentiated colonic adenocarcinoma cells HT29 and proposed that adenosine A(1) receptors might mediate pr oliferative effects. We now extend our investigations to a group of co lonic adenocarcinoma cells at different stages of enterocytic differen tiation. In HT29, DLD-1, Caco-2 and SW403, proliferation was decreased in the presence of adenosine deaminase (5 or 10 U/ml), 5'-N-ethylcarb oxamido-adenosine (NECA; 1 mu M), xanthine amine congener and 8-phenyl theophylline (both at 1 nM or 1 mu M). NECA stimulated cAMP accumulati on in all cell lines except for HT29. In the presence of forskolin (ad enyl cyclase activator) cAMP accumulation was inhibited at sub-nanomol ar concentrations of NECA and stimulated at micromolar concentrations in all four cell lines. The inhibitory response disappeared in the pre sence of 50 nM cyclopentyladenosine (CPA). The binding of [H-3]cyclope ntyl-1,3-dipropylxanthine and [H-3]NECA was also investigated in the f our cell lines. Results of displacement experiments were consistent wi th the idea that poorly differentiated cells with high proliferation r ates (e.g. HT29) express mainly adenosine A(1) receptors. In contrast, displacement curves with more differentiated cells exhibiting low pro liferation rates (e.g. Caco-2, DLD-1, SW403) displayed two components. The high-affinity component was no longer seen in competition experim ents performed in the presence of [H-3]NECA and 50 nM CPA. Together, o ur results further support the idea that extracellular adenosine stimu lates cell proliferation in colonic adenocarcinoma cells. The effects might involve cAMP-coupled adenosine receptors. (C) 1998 Elsevier Scie nce B.V.