This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Recent studies from our laboratory have demonstrated high levels of nicotinic receptors (nAChR) in airway epithelial cells, pulmonary neuroendocrine cells (PNEC) and pulmonary type II cells. Since these cell types are related to the origin of squamous cell carcinomas (SCC), small cell lung carcinomas (SCLC), bronchoalveolar carcinomas (BAC), respectively, it is highly likely that these carcinomas will also express nAChR. Since the nAChR is a ligand-gated ion channel that leads to increased intracellular cellular calcium, activation of these receptors typically stimulates cellular growth. Adding further significance is the recent observation from our laboratory that these cell types also make acetylcholine, the ligand for the nAChR. This suggests an autocrine loop in which lung cancers secrete acetylcholine to stimulate their own growth. While the expression of nicotinic receptors in SCLC has been previously studied and nicotine has been clearly shown to stimulate growth of SCLC, our observation that SCLC may make acetylcholine and hence modulate their own growth is a new and exciting observation. How exogenous ligand (i.e., nicotine from smoking) then interacts with the growth promoting effects of endogenous ligand (acetylcholine) becomes a very interesting question. Thus the purpose of this pilot study is to determine if SCLC, SCC and BAC express acetylcholine, which subtypes of nAChR they express and the effect of nicotinic agonists and antagonists on their growth. This study will generate data relevant to possible treatments of lung cancer, classifications of lung cancer, identification of new tumor markers that may help stratify lung cancer for treatment choices, and new findings about the interaction between lung cancer growth and smoking.
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