Elsevier

Neoplasia

Volume 14, Issue 12, December 2012, Pages 1164-1177, IN24-IN31
Neoplasia

E-cadherin Controls Bronchiolar Progenitor Cells and Onset of Preneoplastic Lesions in Mice1,2

https://doi.org/10.1593/neo.121088Get rights and content
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open access

Although progenitor cells of the conducting airway have been spatially localized and some insights have been gained regarding their molecular phenotype, relatively little is known about the mechanisms regulating their maintenance, activation, and differentiation. This study investigates the potential roles of E-cadherin in mouse Clara cells, as these cells were shown to represent the progenitor/stem cells of the conducting airways and have been implicated as the cell of origin of human non-small cell lung cancer. Postnatal inactivation of E-cadherin affected Clara cell differentiation and compromised airway regeneration under injury conditions. In steady-state adult lung, overexpression of the dominant negative E-cadherin led to an expansion of the bronchiolar stem cells and decreased differentiation concomitant with canonical Wnt signaling activation. Expansion of the bronchiolar stem cell pool was associated with an incessant proliferation of neuroepithelial body.associated Clara cells that ultimately gave rise to bronchiolar hyperplasia. Despite progressive hyperplasia, only a minority of the mice developed pulmonary solid tumors, suggesting that the loss of E-cadherin function leads to tumor formation when additional mutations are sustained. The present study reveals that E-cadherin plays a critical role in the regulation of proliferation and homeostasis of the epithelial cells lining the conducting airways.

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1

Financial Support: Deutsche Krebshilfe Foundation (grant 109081) and German Center for Lung Research (DZL). Conflicts of interest: No potential conflicts of interest declared.

2

This article refers to supplementary materials, which are designated by Figures W1 to W8 and are available online at www.neoplasia.com.

3

Current address: Beatson Institute for Cancer Research, Glasgow, United Kingdom.