Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system

Andreas Weigert, Xiang Zheng, Alina Nenzel, Kati Turkowski, Stefan Günther, Elisabeth Strack, Evelyn Sirait-Fischer, Eiman Elwakeel, Ivan M. Kur, Vandana S. Nikam, Chanil Valasarajan, Hauke Winter, Alexander Wissgott, Robert Voswinkel, Friedrich Grimminger, Bernhard Brüne, Werner Seeger, Soni Savai Pullamsetti and Rajkumar Savai ()
Additional contact information
Andreas Weigert: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
Xiang Zheng: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Alina Nenzel: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Kati Turkowski: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Stefan Günther: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Elisabeth Strack: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
Evelyn Sirait-Fischer: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
Eiman Elwakeel: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
Ivan M. Kur: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
Vandana S. Nikam: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Chanil Valasarajan: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Hauke Winter: Thorax klinik at the University Hospital Heidelberg
Alexander Wissgott: Justus-Liebig University Giessen, Member of the DZL, Member of CPI
Robert Voswinkel: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Friedrich Grimminger: Justus-Liebig University Giessen, Member of the DZL, Member of CPI
Bernhard Brüne: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
Werner Seeger: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Soni Savai Pullamsetti: Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
Rajkumar Savai: Goethe University, and German Cancer Consortium (DKTK), Partner Site Frankfurt

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: Abstract Fibrocytes are bone marrow–derived monocytic cells implicated in wound healing. Here, we identify their role in lung cancer progression/ metastasis. Selective manipulation of fibrocytes in mouse lung tumor models documents the central role of fibrocytes in boosting niche features and enhancing metastasis. Importantly, lung cancer patients show increased number of circulating fibrocytes and marked fibrocyte accumulation in the cancer niche. Using double and triple co-culture systems with human lung cancer cells, fibrocytes, macrophages and endothelial cells, we substantiate the central features of cancer-supporting niche: enhanced cancer cell proliferation and migration, macrophage activation, augmented endothelial cell sprouting and fibrocyte maturation. Upregulation of endothelin and its receptors are noted, and dual endothelin receptor blockade suppresses all cancer-supportive phenotypic alterations via acting on fibrocyte interaction with the cancer niche. We thus provide evidence for a crucial role of fibrocytes in lung cancer progression and metastasis, suggesting targets for treatment strategies.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33458-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33458-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33458-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().