IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33458-8.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33458-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33458-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Fayang Ma & Kyle Laster & Zigang Dong, 2022. "The comparison of cancer gene mutation frequencies in Chinese and U.S. patient populations," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Yao-Zhong Liu & Charles A Miller & Yan Zhuang & Sudurika S Mukhopadhyay & Shigeki Saito & Edward B. Overton & Gilbert F Morris, 2020. "The Impact of the Deepwater Horizon Oil Spill upon Lung Health—Mouse Model-Based RNA-Seq Analyses," IJERPH, MDPI, vol. 17(15), pages 1-23, July.
    3. Fernando C. Baltanás & Rósula García-Navas & Pablo Rodríguez-Ramos & Nuria Calzada & Cristina Cuesta & Javier Borrajo & Rocío Fuentes-Mateos & Andrea Olarte-San Juan & Nerea Vidaña & Esther Castellano, 2023. "Critical requirement of SOS1 for tumor development and microenvironment modulation in KRASG12D-driven lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. François Virard & Stéphane Giraud & Mélanie Bonnet & Léa Magadoux & Laetitia Martin & Thuy Ha Pham & Najwa Skafi & Sophie Deneuve & Rita Frem & Bruno O. Villoutreix & Nawal Hajj Sleiman & Jonathan Reb, 2024. "Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Wenbin Xu & Han Yao & Zhen Wu & Xiaojun Yan & Zishan Jiao & Yajing Liu & Meng Zhang & Donglai Wang, 2024. "Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33458-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.