title: Adenosine modulates cell proliferation in human colonic carcinoma. II. Differential behavior of HT29, DLD-1, Caco-2 and SW403 cell lines.
abstract: In a previous study, we provided evidence that extracellular adenosine modulates growth of the poorly differentiated colonic adenocarcinoma cells HT29 and proposed that adenosine A1 receptors might mediate proliferative effects. We now extend our investigations to a group of colonic adenocarcinoma cells at different stages of enterocytic differentiation. In HT29, DLD-1, Caco-2 and SW403, proliferation was decreased in the presence of adenosine deaminase (5 or 10 U/ml), 5'-N-ethylcarboxamido-adenosine (NECA; 1 microM), xanthine amine congener and 8-phenyltheophylline (both at 1 nM or 1 microM). NECA stimulated cAMP accumulation in all cell lines except for HT29. In the presence of forskolin (adenyl cyclase activator) cAMP accumulation was inhibited at sub-nanomolar concentrations of NECA and stimulated at micromolar concentrations in all four cell lines. The inhibitory response disappeared in the presence of 50 nM cyclopentyladenosine (CPA). The binding of [3H]cyclopentyl-1,3-dipropylxanthine and [3H]NECA was also investigated in the four cell lines. Results of displacement experiments were consistent with the idea that poorly differentiated cells with high proliferation rates (e.g. HT29) express mainly adenosine A receptors. In contrast, displacement curves with more differentiated cells exhibiting low proliferation rates (e.g. Caco-2, DLD-1, SW403) displayed two components. The high-affinity component was no longer seen in competition experiments performed in the presence of [3H]NECA and 50 nM CPA. Together, our results further support the idea that extracellular adenosine stimulates cell proliferation in colonic adenocarcinoma cells. The effects might involve cAMP-coupled adenosine receptors.
authors.affiliation: Laboratoire de Biologie des Interactions Cellulaires, CNRS UMR 6558, Université de Poitiers, France.
authors.forename: V
authors.initials: V
authors.lastname: Lelièvre
authors.forename: J M
authors.initials: JM
authors.lastname: Muller
authors.forename: J
authors.initials: J
authors.lastname: Falcòn
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000502:physiology; D000243:Adenosine Deaminase / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001667:Binding, Competitive; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D019073:HT29 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000243:Adenosine Deaminase; D000241:Adenosine