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- Title
Adenosine receptors in colon carcinoma tissues and colon tumoral cell lines: Focus on the A<sub>3</sub> adenosine subtype.
- Authors
Gessi, Stefania; Merighi, Stefania; Varani, Katia; Cattabriga, Elena; Benini, Annalisa; Mirandola, Prisco; Leung, Edward; Lennan, Stephen Mac; Feo, Carlo; Baraldi, Stefania; Borea, Pier Andrea
- Abstract
Adenosine may affect several pathophysiological processes, including cellular proliferation, through interaction with A1, A2A, A2B, and A3 receptors. In this study we characterized adenosine receptors in human colon cancer tissues and in colon cancer cell lines Caco2, DLD1, HT29. mRNA of all adenosine subtypes was detected in cancer tissues and cell lines. At a protein levels low amount of A1, A2A, and A2B receptors were detected, whilst the A3 was the most abundant subtype in both cancer tissues and cells, with a pharmacological profile typical of the A3 subtype. All the receptors were coupled to stimulation/inhibition of adenylyl-cyclase in cancer cells, with the exception of A1 subtype. Adenosine increased cell proliferation with an EC50 of 3–12 µM in cancer cells. This effect was not essentially reduced by adenosine receptor antagonists. However dypiridamol, an adenosine transport inhibitor, increased the stimulatory effect induced by adenosine, suggesting an action at the cell surface. Addition of adenosine deaminase makes the A3 agonist 2-chloro-N6-(3-iodobenzyl)-N-methyl-5′-carbamoyladenosine (Cl-IB-MECA) able to stimulate cell proliferation with an EC50 of 0.5–0.9 nM in cancer cells, suggesting a tonic proliferative effect induced by endogenous adenosine. This effect was antagonized by 5-N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2(2furyl)-pyrazolo-[4,3e]-1,2,4-triazolo [1,5-c] pyrimidine (MRE 3008F20) 10 nM. Cl-IB-MECA-stimulated cell proliferation involved extracellular-signal-regulated-kinases (ERK1/2) pathway, as demonstrated by reduction of proliferation with 1,4-diamino-2,3-dicyano-1,4-bis-[2-amino-phenylthio]-butadiene (U0126) and by ERK1/2 phosphorylation. In conclusion this study indicates for the first time that in colon cancer cell lines endogenous adenosine, through the interaction with A3 receptors, mediates a tonic proliferative effect. J. Cell. Physiol. 211: 826–836, 2007. © 2007 Wiley-Liss, Inc.
- Subjects
ADENOSINES; COLON cancer; CANCER cells; TUMORS; PHARMACOLOGY
- Publication
Journal of Cellular Physiology, 2007, Vol 211, Issue 3, p826
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.20994