TY - JOUR T1 - Implication of adamalysin proteases in mesothelioma JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2015.OA5006 VL - 46 IS - suppl 59 SP - OA5006 AU - Christelle Sepult AU - Natacha Rocks AU - Sandrine Bekaert AU - Kim Donati AU - Bernard Duysinx AU - Agnes Noel AU - Didier Cataldo Y1 - 2015/09/01 UR - http://erj.ersjournals.com/content/46/suppl_59/OA5006.abstract N2 - The main risk factor for malignant pleural mesothelioma (MPM) is asbestos fibers exposure but mechanisms that preclude malignant transformation are not totally elucidated.The implication of ADAM/TS (A Disintegrin And Metalloprotease/with ThromboSpondin motifs) has been previously unveiled in several cancers. We aimed to determine the potential importance of ADAM/TS in mesothelioma progression.We used a mouse model based on orthotopic injection of AB12 cell line (murine malignant mesothelioma cell line). BALB/C mice were intrapleurally injected with AB12 cells and tumors developed in the pleural space showed an increase of ADAM-8 and -10 expressions as compared to cultured AB12.We also developed a mouseprimary cancerization model induced by repeated intraperitoneal injections of crocidolite fibers. After one year, primary mesothelioma cell lines were harvested from these animals. These primary mesothelioma cell lines were injected in pleura of syngeneic animals and displayed an increase of ADAM-8 expression as compared to cultured cells.Twelve human samples of MPM were screened and showed significant increase of ADAM-8 and -10 expressions as compared to matched non-diseased pleural samples.In vitro targeted inhibition studies: showed that ADAM8 depletion decreases MPM cells migration in a wound-healing assay.In conclusion, these results identify ADAM8 as a potential target in mesothelioma. ER -