Inhibition of the met receptor in mesothelioma.

摘要: Background: Expression of the Met receptor and its ligand, hepatocyte growth factor (HGF), has been observed in 74% to 100% 40% 85% malignant pleural mesothelioma (MPM) specimens, respectively. HGF stimulation shown enhance MPM cell proliferation, migration, scattering, invasiveness. Experimental Design: To investigate a potential therapeutic role for MPM, we examined effects PHA-665752, specific small-molecule inhibitor tyrosine kinase, panel 10 lines. Results: Two lines, H2461 JMN-1B, exhibited autocrine production as measured by ELISA (3.9 10.5 ng/mL, respectively, versus 50 1 2 μmol/L, No activating mutations were detected any Consistent with inhibition, PHA-665752 caused cycle arrest at G -S boundary accompanied dose-dependent decrease phosphorylation Met, p70S6K, Akt, extracellular signal-regulated kinase 1/2. Growth cells was also inhibited neutralizing antibodies RNA interference knockdown receptor, confirming that inhibition through Met-dependent mechanism. reduced vitro migration invasion. Conclusions: Taken together, these findings suggest may be an effective strategy patients provides mechanism, presence HGF/Met loop, which select treatment.