RT Journal Article
SR Electronic
T1 Implication of adamalysin proteases in mesothelioma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP OA5006
DO 10.1183/13993003.congress-2015.OA5006
VO 46
IS suppl 59
A1 Christelle Sepult
A1 Natacha Rocks
A1 Sandrine Bekaert
A1 Kim Donati
A1 Bernard Duysinx
A1 Agnes Noel
A1 Didier Cataldo
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/OA5006.abstract
AB 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.