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

Author

Listed:
  • Andreas Weigert

    (Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
    Goethe University, and German Cancer Consortium (DKTK), Partner Site Frankfurt)

  • 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
    Justus Liebig University)

  • Bernhard Brüne

    (Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I
    Goethe University, and German Cancer Consortium (DKTK), Partner Site Frankfurt)

  • 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)
    Justus-Liebig University Giessen, Member of the DZL, Member of CPI
    Justus Liebig University)

  • 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)
    Justus-Liebig University Giessen, Member of the DZL, Member of CPI
    Justus Liebig University)

  • Rajkumar Savai

    (Goethe University, and German Cancer Consortium (DKTK), Partner Site Frankfurt
    Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI)
    Justus-Liebig University Giessen, Member of the DZL, Member of CPI
    Justus Liebig University)

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.

Suggested Citation

  • 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, 2022. "Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33458-8
    DOI: 10.1038/s41467-022-33458-8
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    References listed on IDEAS

    as
    1. Leisa Johnson & Kim Mercer & Doron Greenbaum & Roderick T. Bronson & Denise Crowley & David A. Tuveson & Tyler Jacks, 2001. "Somatic activation of the K-ras oncogene causes early onset lung cancer in mice," Nature, Nature, vol. 410(6832), pages 1111-1116, April.
    2. Atsushi Mitsuhashi & Hisatsugu Goto & Atsuro Saijo & Van The Trung & Yoshinori Aono & Hirokazu Ogino & Takuya Kuramoto & Sho Tabata & Hisanori Uehara & Keisuke Izumi & Mitsuteru Yoshida & Hiroaki Koba, 2015. "Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab," Nature Communications, Nature, vol. 6(1), pages 1-15, December.
    3. Grit S. Herter-Sprie & Houari Korideck & Camilla L. Christensen & Jan M. Herter & Kevin Rhee & Ross I. Berbeco & David G. Bennett & Esra A. Akbay & David Kozono & Raymond H. Mak & G. Mike Makrigiorgos, 2014. "Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
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