Abstract 1041 The Role of Nicotine, BDNF, and β-Adrenergic Receptor Ligands in Regulating Soluble E-Cadherin Signaling in Non-Small-Cell Lung Cancer Cells

The ectodomain of E-cadherin can be cleaved and released as soluble E-cadherin (sE-cad).Matrix metalloprotease 9 (MMP9) is among the proteases implicated in this cleavage.Treatment of non-small cell lung cancer (NSCLC) cell lines, A549 and H1299, with brain-derived neurotrophic factor (BDNF), nicotine, or epinephrine increased MMP9 levels in the media while cell treatment with the b-adrenergic receptor blocker, propranolol, decreased those levels.Increased sE-cad levels in A549 cell media correlated with increased MMP9 levels and decreased upon knockdown of MMP9.While no effects were found using H1299 cells, immunodepletion of sEcad from the media of A549 cells untreated or treated with BDNF, nicotine, or epinephrine decreased activation of epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2), increased the activity of p53, enhanced apoptosis, and decreased cell viability.