EpCAM+CD73+ mark epithelial progenitor cells in postnatal human lung and is associated with pathogenesis of pulmonary disease including lung adenocarcinoma.

Wang, Limei; Dorn, Patrick; Simillion, Cedric; Froment, Laurène; Berezowska, Sabina Anna; Tschanz, Stefan A.; Haenni, Beat; Blank, Fabian; Wotzkow, Carlos; Peng, Ren-Wang; Marti, Thomas; Bode, Peter Karl; Moehrlen, Ueli; Schmid, Ralph; Hall, Sean (2020). EpCAM+CD73+ mark epithelial progenitor cells in postnatal human lung and is associated with pathogenesis of pulmonary disease including lung adenocarcinoma. American journal of physiology - lung cellular and molecular physiology, 319(5), L794-L809. American Physiological Society 10.1152/ajplung.00279.2019

[img] Text
Blank F et all_EpCAM.pdf - Accepted Version
Restricted to registered users only until 29 July 2021.
Available under License Publisher holds Copyright.

Download (4MB) | Request a copy

Lung injury in mice induces mobilization of discrete subsets of epithelial progenitor cells to promote new airway and alveolar structures. However, whether similar cell types exist in human lung remains unresolved. Using flow cytometry, we identified a distinct cluster of cells expressing epithelial cell adhesion molecule (EpCAM), a cell surface marker expressed on epithelial progenitor cells, enriched in the ecto-5'-nucleotidase CD73 in unaffected postnatal human lung resected from pediatric patients with congenital lung lesions. Within the EpCAM+CD73+ population, a small subset co-express integrin β4 and HTII-280. This population remained stable with age. Spatially, EpCAM+CD73+ cells were positioned along the basal membrane of respiratory epithelium and alveolus next to CD73+ cells lacking EpCAM. Expanded EpCAM+CD73+ cells give rise to pseudostratified epithelium in 2D air-liquid interface or a clonal 3D organoid assay. Organoids generated under alveolar differentiation conditions were cystic-like and lacked robust alveolar mature cell types. Compared with unaffected postnatal lung, congenital lung lesions were marked by clusters of EpCAM+CD73+ cells in airway and cystic distal lung structures lined by simple epithelium of composed of EpCAM+SCGB1A1+ cells and hyperplastic EpCAM+proSPC+ cells. In non-small cell lung cancer (NSCLC), there was a marked increase in EpCAM+CD73+ tumor cells enriched in inhibitory immune checkpoint molecules CD47 and programmed death-ligand 1 (PD-L1), which was associated with poor survival in lung adenocarcinoma. In conclusion, EpCAM+CD73+ cells are a rare novel epithelial progenitor cell in human lung. Importantly, re-emergence of CD73 in lung adenocarcinoma enriched in negative immune checkpoint molecules may serve as a novel therapeutic target.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Live Cell Imaging (LCI)

UniBE Contributor:

Wang, Limei; Dorn, Patrick; Froment, Laurène; Berezowska, Sabina Anna; Tschanz, Stefan A.; Haenni, Beat; Blank, Fabian; Wotzkow Alvarez, Carlos; Peng, Ren-Wang; Marti, Thomas; Schmid, Ralph and Hall, Sean

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1040-0605

Publisher:

American Physiological Society

Funders:

[42] Schweizerischer Nationalfonds

Language:

English

Submitter:

Heidi Lobsiger

Date Deposited:

24 Aug 2020 10:45

Last Modified:

04 Mar 2021 14:59

Publisher DOI:

10.1152/ajplung.00279.2019

PubMed ID:

32726135

Uncontrolled Keywords:

CD73 EpCAM congenital lung lesions lung cancer organoids

BORIS DOI:

10.7892/boris.145993

URI:

https://boris.unibe.ch/id/eprint/145993

Actions (login required)

Edit item Edit item
Provide Feedback