Functional facets of the pulmonary neuroendocrine system.
Pulmonary neuroendocrine cells (PNECs) have been around for 60 years in the scientific literature, although phylogenetically they are ancient. Their traditionally ascribed functions include chemoreception and regulation of lung maturation and growth. There is recent evidence that neuroendocrine (NE) differentiation in the lung is regulated by genes and pathways that are conserved in the development of the nervous system from Drosophila to humans (such as achaete-scute homolog-1), or implicated in the carcinogenesis of the nervous or NE system (such as the retinoblastoma tumor suppressor gene). In addition, complex neural networks are in place to regulate chemosensory and other functions. Even solitary PNECs appear to be innervated. For the first time ever, we have mouse models for lung NE carcinomas, including the most common and virulent small cell lung carcinoma. Moreover, PNECs may be important for inflammatory responses, and pivotal for lung stem cell niches. These discoveries signify an exciting new era for PNECs and are likely to have therapeutic and diagnostic applications.
Linnoila
R Ilona
RI
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. linnoila@nih.gov
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002628:Chemoreceptor Cells / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000473:pathology; D008168:Lung / Q000196:embryology / Q000294:innervation* / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology; D046568:Neuroepithelial Bodies / Q000166:cytology* / Q000378:metabolism; D009490:Neurosecretory Systems / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D051880:Receptors, Notch; C065500:ASCL1 protein, human