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Published ahead of print on December 7, 2006, doi:10.1164/rccm.200607-984PP

Am. J. Respir. Crit. Care Med., Volume 175, Number 6, March 2007, 547-553

A more recent version of this article appeared on March 15, 2007
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Submitted on July 19, 2006
Accepted on December 7, 2006

Lung Cancer and Lung Stem Cells: Strange Bedfellows?

Adam Giangreco1, Karen R Groot2, and Sam M Janes2*

1 Keratinocyte Laboratory, Cancer Research UK, London, United Kingdom, 2 Centre of Respiratory Research, University College London, London, United Kingdom

* To whom correspondence should be addressed. E-mail: s.janes{at}ucl.ac.uk.

Lung cancer is a significant disease with survival rates remaining poor despite numerous therapeutic advances during the last thirty years. Understanding lung cancer pathogenesis through murine modelling may improve future human therapies and new data indicates that mutations within different endogenous stem cells situated throughout airways can drive cancer formation. Airway stem cells maintain proto-tumorigenic characteristics including high proliferative capacity, multipotent differentiation, and a long lifespan relative to other cells. These cells localise to proximal airway submucosal glands / intercartilagenous rings, neuroepithelial bodies, and terminal bronchioles / bronchoalveolar duct junctions. Recent studies suggest that endogenous stem cell signalling and differentiation pathways are maintained within distinct cancer types, and that destabilization of this signalling machinery may initiate region-specific lung cancers. A better understanding of this relationship between stem cell regulation, cellular mutation, and lung cancer oncogenesis is critical for developing the next wave of lung cancer therapies.
Key words: Lung Cancer, Stem Cells, Pathogenesis, Signalling, Progenitors




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