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

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10.1038_s41467-022-33458-8.pdf (9.517Mb)
Date
2022
Author
Weigert, Andreas
Zheng, Xiang
Nenzel, Alina
Turkowski, Kati
Günther, Stefan
Strack, Elisabeth
Sirait-Fischer, Evelyn
Elwakeel, Eiman
Kur, Ivan M.
Nikam, Vandana S.
Valasarajan, Chanil
Winter, Hauke
Wissgott, Alexander
Voswinkel, Robert
Grimminger, Friedrich
Brüne, Bernhard
Seeger, Werner
Pullamsetti, Soni Savai
Savai, Rajkumar
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http://dx.doi.org/10.22029/jlupub-15592
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.

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Nature Communications 13 (2022), 1-21, 6078

URI of original publication
https://doi.org/10.1038/s41467-022-33458-8
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