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

Weigert, A., Zheng, X., Nenzel, A., Turkowski, K., Guenther, S., Strack, E., et al. (2022). Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system. NATURE COMMUNICATIONS, 13(1): 6078. doi:10.1038/s41467-022-33458-8.

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 Creators:
Weigert, Andreas, Author
Zheng, Xiang1, Author           
Nenzel, Alina2, Author           
Turkowski, Kati1, Author           
Guenther, Stefan3, Author           
Strack, Elisabeth, Author
Sirait-Fischer, Evelyn, Author
Elwakeel, Eiman, Author
Kur, Ivan M., Author
Nikam, Vandana S.1, Author           
Valasarajan, Chanil1, Author           
Winter, Hauke, Author
Wissgott, Alexander, Author
Voswinkel, Robert, Author
Grimminger, Friedrich, Author
Brune, Bernhard, Author
Seeger, Werner1, Author           
Pullamsetti, Soni Savai1, Author           
Savai, Rajkumar1, Author           
Affiliations:
1Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              
2Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2324692              
3Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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 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.
Fibrocytes are monocyte-derived cells implicated in wound healing. Here, the authors utilise single cell RNA-seq, genetic ablation and multiplexed imaging to identify a fibrocyte population in lung cancer models, and use human lung cancer coculture systems to highlight their potential to modulate microenvironmental niche and sensitivity to endothelin blockade.

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 Dates: 2022-10-14
 Publication Status: Published online
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 Identifiers: ISI: 000874078500008
DOI: 10.1038/s41467-022-33458-8
PMID: 36241617
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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Pages: - Volume / Issue: 13 (1) Sequence Number: 6078 Start / End Page: - Identifier: -