Document Detail

A3 Receptors Are Overexpressed in Pleura from Patients with Mesothelioma and Reduce Cell Growth via Akt/Nuclear Factor-{kappa}B Pathway.
MedLine Citation:
PMID:  20870754     Owner:  NLM     Status:  In-Data-Review    
Rationale: A strong link has been established between exposure to asbestos and increased risk for pleural malignant mesothelioma (MM). Adenosine plays a key role in inflammatory processes and cancer, where it is involved in the regulation of cell death and proliferation. Objectives: The primary aim of this study was to investigate the presence of adenosine receptors (ARs) in human MM pleura (MMP) and healthy mesothelial pleura (HMP). To shed some light on the interaction between adenosine and MM, the presence and functionality of ARs were explored in human healthy mesothelial cells (HMC) and in malignant mesothelioma cells (MMC). Methods: ARs were analyzed by using reverse transcriptase-polymerase chain reaction, Western blotting, and saturation binding assays. HMC were treated with crocidolite asbestos, which is the principal risk factor for MM. The role of A(3)ARs on these cellular models, evaluating cAMP production, Akt phosphorylation, and nuclear factor (NF)-κB activation, was investigated. The dual effect of A(3)AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis, and cytotoxicity assays. Measurements and Main Results: A(3)AR was up-regulated by 2.5-fold (P < 0.01) in MMP when compared with HMP. Stimulation of A(3)ARs decreased proliferation and exerted a cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and tumor necrosis factor-α, but not on HMC with an involvement of the deregulation of Akt/NF-κB cell survival pathway. Conclusions: These new findings suggest that A(3)AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full-blown MM.
Katia Varani; Stefania Maniero; Fabrizio Vincenzi; Martina Targa; Angela Stefanelli; Pio Maniscalco; Fernanda Martini; Mauro Tognon; Pier Andrea Borea
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Publication Detail:
Type:  Journal Article     Date:  2010-09-24
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  183     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  522-30     Citation Subset:  AIM; IM    
Department of Clinical and Experimental Medicine, Pharmacology Unit, University of Ferrara, via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
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