S60 Mesenchymal stem cells expressing TRAIL induce apoptosis in malignant pleural mesothelioma

Abstract

clustering with ability to identify upregulation of cancer specific genes in malignant relative to benign nodes (notably EGFR, HGFR/ c-met and HER2 were among genes most upregulated). Conclusion We demonstrate the feasibility of RNA extraction and GEP on EBUS-derived lymph node cytological aspirates and show differences in gene expression profiles between benign and tumourinfiltrated lymph node mRNA. Further studies on larger patient cohorts are necessary to identify expression profiles that can robustly differentiate benign from malignant lymph nodes in NSCLC. Human lung cancers including squamous cell carcinoma (SCC) are a leading cause of death, and while evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show that bcatenin signalling regulates basal stem cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal stem cell b-catenin signalling is positively associated with increased disease severity, epithelial proliferation, and reduced intercellular adhesiveness. We demonstrate that transgene-mediated b-catenin inhibition within keratin 14-expressing basal stem cells delayed normal airway repair while basal cell-specific b-catenin activation increased cell proliferation, directed differentiation, and promoted an epithelial-to-mesenchymal transition (EMT) that included increased Snail transcription and reduced E-cadherin-mediated adhesiveness. These effects were recapitulated in normal human bronchial epithelial cells in vitro following both pharmacological bcatenin activation and E-cadherin inhibition, and mirrored our findings in preinvasive SCCs. Overall this data shows that airway stem cell b-catenin modulates cell adhesiveness to determine cell fate and its mis-expression is a key step in the development of human lung cancer. S58 BETA-CATENIN DETERMINES TRACHEAL CELL FATE AND SQUAMOUS LUNG CANCER PROGRESSION BY MODULATING INTERCELLULAR ADHESIVENESS