E-Cadherin Controls Bronchiolar Progenitor Cells and Onset of Preneoplastic Lesions in Mice

Please always quote using this URN: urn:nbn:de:bvb:20-opus-135407
  • 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 ofAlthough 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.show moreshow less

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Metadaten
Author: Fatih Ceteci, Semra Ceteci, Emanuele Zanucco, Chitra Thakur, Matthias Becker, Nefertiti El-Nikhely, Ludger Fink, Werner Seeger, Rajkumar Savai, Ulf R. Rapp
URN:urn:nbn:de:bvb:20-opus-135407
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Medizinische Strahlenkunde und Zellforschung
Language:English
Parent Title (English):Neoplasia
Year of Completion:2012
Volume:14
Issue:12
Pagenumber:1164–1177
Source:Neoplasia (2012) 14, 1164–1177. DOI 10.1593/neo.121088
DOI:https://doi.org/10.1593/neo.121088
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:airway; basal cell; clara cell; epithelium; gene expression; in vivo; injury; lung cancer; renewal; stem cells
Release Date:2018/03/29
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung