This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Recent studies from our laboratory have demonstrated high levels of nicotinic receptors (nAChR) and muscarinic receptors (mAChR) 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 and mAChR. Since activation of these receptors leads to increased intracellular cellular calcium, their activation typically stimulates cellular growth. Adding further significance is the recent observation from our laboratory that these cell types also make acetylcholine, the ligand for both nAChR and mAChR. 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. Hence, how exogenous ligand (i.e., nicotine from smoking) then interacts with the growth promoting effects of endogenous ligand (acetylcholine) becomes a very important question. Thus the purpose of this study is to determine if SCLC, SCC and BAC express acetylcholine, nAChR and mAChR and to then determine the potential for antagonists of cholinergic signaling to provide new approaches to blocking the growth and development of lung cancer. Progress in the current year has demonstrated potential utility for M3 muscarinic antagonists to inhibit lung cancer growth.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-52
Application #
8357740
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
52
Fiscal Year
2011
Total Cost
$58,239
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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