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Published ahead of print on December 7, 2006, doi:10.1164/rccm.200607-984PP
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American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 547-553, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200607-984PP

Pulmonary Perspective

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; and 2 Centre of Respiratory Research, University College London, London, United Kingdom

Correspondence and requests for reprints should be addressed to Sam M. Janes, M.D., Ph.D., Centre of Respiratory Research, Rayne Building, University College London, 5 University Street, London, WC1E 6JJ UK. E-mail: s.janes{at}ucl.ac.uk

ABSTRACT

Lung cancer is a significant disease with survival rates remaining poor despite numerous therapeutic advances during the last 30 years. Understanding lung cancer pathogenesis through murine modeling may improve future human therapies, and new data indicate that mutations within different endogenous stem cells situated throughout airways can drive cancer formation. Airway stem cells maintain prototumorigenic characteristics, including high proliferative capacity, multipotent differentiation, and a long lifespan relative to other cells. These cells localize to proximal airway submucosal glands/intercartilagenous rings, neuroepithelial bodies, and terminal bronchioles/bronchoalveolar duct junctions. Recent studies suggest that endogenous stem cell signaling and differentiation pathways are maintained within distinct cancer types, and that destabilization of this signaling machinery may initiate region-specific lung cancers. A better understanding of this relationship among 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 • signaling • progenitors




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