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 RT-PCR, western blotting and saturation binding assays. HMC were treated with crocidolite asbestos, which is the principal risk factor of MM. The role of A3ARs on these cellular models, evaluating cAMP production, Akt phosphorylation and NF-kB activation was investigated. The dual effect of A3AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis and cytotoxicity assays. MEASUREMENTS AND MAIN RESULTS: A3AR was up-regulated by 2.5 fold (P<0.01) in MMP when compared with HMP. Stimulation of A3ARs decreased proliferation and exerted a cytotoxic and pro-apoptotic effect on MMC and on HMC exposed to asbestos and TNF-α, but not on HMC with an involvement of the de-regulation of Akt/NF-kB cell survival pathway. CONCLUSION: These new findings suggest that A3AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full blown MM.

A3 Receptors are Overexpressed in Pleura from Mesothelioma Patients and Reduce Cell Growth via Akt/NF-kB Pathway.

VARANI, Katia;MANIERO, Stefania;VINCENZI, Fabrizio;TARGA, Martina;STEFANELLI, Angela;MANISCALCO, Pio;MARTINI, Fernanda;TOGNON, Mauro;BOREA, Pier Andrea
2011

Abstract

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 RT-PCR, western blotting and saturation binding assays. HMC were treated with crocidolite asbestos, which is the principal risk factor of MM. The role of A3ARs on these cellular models, evaluating cAMP production, Akt phosphorylation and NF-kB activation was investigated. The dual effect of A3AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis and cytotoxicity assays. MEASUREMENTS AND MAIN RESULTS: A3AR was up-regulated by 2.5 fold (P<0.01) in MMP when compared with HMP. Stimulation of A3ARs decreased proliferation and exerted a cytotoxic and pro-apoptotic effect on MMC and on HMC exposed to asbestos and TNF-α, but not on HMC with an involvement of the de-regulation of Akt/NF-kB cell survival pathway. CONCLUSION: These new findings suggest that A3AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full blown MM.
Varani, Katia; Maniero, Stefania; Vincenzi, Fabrizio; Targa, Martina; Stefanelli, Angela; Maniscalco, Pio; Martini, Fernanda; Tognon, Mauro; Borea, Pier Andrea
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1403605
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 44
  • ???jsp.display-item.citation.isi??? 38
social impact