IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-022-35701-8.html
   My bibliography  Save this article

In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma

Author

Listed:
  • Seiji Taniguchi

    (Osaka University Graduate School of Medicine
    WPI-Immunology Frontier Research Center, Osaka University
    Osaka University Graduate School of Medicine)

  • Takahiro Matsui

    (Osaka University Graduate School of Medicine
    Osaka University Graduate School of Medicine)

  • Kenji Kimura

    (Osaka University Graduate School of Medicine)

  • Soichiro Funaki

    (Osaka University Graduate School of Medicine)

  • Yu Miyamoto

    (Osaka University Graduate School of Medicine
    WPI-Immunology Frontier Research Center, Osaka University)

  • Yutaka Uchida

    (Osaka University Graduate School of Medicine
    WPI-Immunology Frontier Research Center, Osaka University)

  • Takao Sudo

    (Osaka University Graduate School of Medicine
    WPI-Immunology Frontier Research Center, Osaka University)

  • Junichi Kikuta

    (Osaka University Graduate School of Medicine
    WPI-Immunology Frontier Research Center, Osaka University
    National Institutes of Biomedical Innovation, Health and Nutrition)

  • Tetsuya Hara

    (Kobe Pharmaceutical University)

  • Daisuke Motooka

    (Research Institute for Microbial Diseases, Osaka University
    WPI-Immunology Frontier Research Center, Osaka University)

  • Yu-Chen Liu

    (WPI-Immunology Frontier Research Center, Osaka University)

  • Daisuke Okuzaki

    (Research Institute for Microbial Diseases, Osaka University
    WPI-Immunology Frontier Research Center, Osaka University)

  • Eiichi Morii

    (Osaka University Graduate School of Medicine)

  • Noriaki Emoto

    (Kobe Pharmaceutical University)

  • Yasushi Shintani

    (Osaka University Graduate School of Medicine)

  • Masaru Ishii

    (Osaka University Graduate School of Medicine
    WPI-Immunology Frontier Research Center, Osaka University
    National Institutes of Biomedical Innovation, Health and Nutrition)

Abstract

Alveolar macrophages (AMs) are crucial for maintaining normal lung function. They are abundant in lung cancer tissues, but their pathophysiological significance remains unknown. Here we show, using an orthotopic murine lung cancer model and human carcinoma samples, that AMs support cancer cell proliferation and thus contribute to unfavourable outcome. Inhibin beta A (INHBA) expression is upregulated in AMs under tumor-bearing conditions, leading to the secretion of activin A, a homodimer of INHBA. Accordingly, follistatin, an antagonist of activin A is able to inhibit lung cancer cell proliferation. Single-cell RNA sequence analysis identifies a characteristic subset of AMs specifically induced in the tumor environment that are abundant in INHBA, and distinct from INHBA-expressing AMs in normal lungs. Moreover, postnatal deletion of INHBA/activin A could limit tumor growth in experimental models. Collectively, our findings demonstrate the critical pathological role of activin A-producing AMs in tumorigenesis, and provides means to clearly distinguish them from their healthy counterparts.

Suggested Citation

  • Seiji Taniguchi & Takahiro Matsui & Kenji Kimura & Soichiro Funaki & Yu Miyamoto & Yutaka Uchida & Takao Sudo & Junichi Kikuta & Tetsuya Hara & Daisuke Motooka & Yu-Chen Liu & Daisuke Okuzaki & Eiichi, 2023. "In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35701-8
    DOI: 10.1038/s41467-022-35701-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35701-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-35701-8?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. Elisa Gomez Perdiguero & Kay Klapproth & Christian Schulz & Katrin Busch & Emanuele Azzoni & Lucile Crozet & Hannah Garner & Celine Trouillet & Marella F. de Bruijn & Frederic Geissmann & Hans-Reimer , 2015. "Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors," Nature, Nature, vol. 518(7540), pages 547-551, February.
    2. Gioele La Manno & Ruslan Soldatov & Amit Zeisel & Emelie Braun & Hannah Hochgerner & Viktor Petukhov & Katja Lidschreiber & Maria E. Kastriti & Peter Lönnerberg & Alessandro Furlan & Jean Fan & Lars E, 2018. "RNA velocity of single cells," Nature, Nature, vol. 560(7719), pages 494-498, August.
    3. María Casanova-Acebes & Erica Dalla & Andrew M. Leader & Jessica LeBerichel & Jovan Nikolic & Blanca M. Morales & Markus Brown & Christie Chang & Leanna Troncoso & Steven T. Chen & Ana Sastre-Perona &, 2021. "Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells," Nature, Nature, vol. 595(7868), pages 578-584, July.
    4. Takashi Satoh & Katsuhiro Nakagawa & Fuminori Sugihara & Ryusuke Kuwahara & Motooki Ashihara & Fumihiro Yamane & Yosuke Minowa & Kiyoharu Fukushima & Isao Ebina & Yoshichika Yoshioka & Atsushi Kumanog, 2017. "Identification of an atypical monocyte and committed progenitor involved in fibrosis," Nature, Nature, vol. 541(7635), pages 96-101, January.
    5. Philippe Mauffrey & Nicolas Tchitchek & Vilma Barroca & Alexis-Pierre Bemelmans & Virginie Firlej & Yves Allory & Paul-Henri Roméo & Claire Magnon, 2019. "Progenitors from the central nervous system drive neurogenesis in cancer," Nature, Nature, vol. 569(7758), pages 672-678, May.
    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. Huanhuan Tan & Weixu Wang & Congjin Zhou & Yanfeng Wang & Shu Zhang & Pinglan Yang & Rui Guo & Wei Chen & Jinwen Zhang & Lan Ye & Yiqiang Cui & Ting Ni & Ke Zheng, 2023. "Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    3. Christoph Ziegenhain & Rickard Sandberg, 2021. "BAMboozle removes genetic variation from human sequence data for open data sharing," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Yoshiaki Yasumizu & Naganari Ohkura & Hisashi Murata & Makoto Kinoshita & Soichiro Funaki & Satoshi Nojima & Kansuke Kido & Masaharu Kohara & Daisuke Motooka & Daisuke Okuzaki & Shuji Suganami & Eriko, 2022. "Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    7. David G. Priest & Takeshi Ebihara & Janyerkye Tulyeu & Jonas N. Søndergaard & Shuhei Sakakibara & Fuminori Sugihara & Shunichiro Nakao & Yuki Togami & Jumpei Yoshimura & Hiroshi Ito & Shinya Onishi & , 2024. "Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    8. Jeff Yat-Fai Chung & Philip Chiu-Tsun Tang & Max Kam-Kwan Chan & Vivian Weiwen Xue & Xiao-Ru Huang & Calvin Sze-Hang Ng & Dongmei Zhang & Kam-Tong Leung & Chun-Kwok Wong & Tin-Lap Lee & Eric W-F Lam &, 2023. "Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Fabian Peisker & Maurice Halder & James Nagai & Susanne Ziegler & Nadine Kaesler & Konrad Hoeft & Ronghui Li & Eric M. J. Bindels & Christoph Kuppe & Julia Moellmann & Michael Lehrke & Christian Stopp, 2022. "Mapping the cardiac vascular niche in heart failure," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    10. Yan Tang & David J. Kwiatkowski & Elizabeth P. Henske, 2022. "Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    11. Jun Dai & Shuyu Zheng & Matías M. Falco & Jie Bao & Johanna Eriksson & Sanna Pikkusaari & Sofia Forstén & Jing Jiang & Wenyu Wang & Luping Gao & Fernando Perez-Villatoro & Olli Dufva & Khalid Saeed & , 2024. "Tracing back primed resistance in cancer via sister cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Ryuki Shimada & Yuzuru Kato & Naoki Takeda & Sayoko Fujimura & Kei-ichiro Yasunaga & Shingo Usuki & Hitoshi Niwa & Kimi Araki & Kei-ichiro Ishiguro, 2023. "STRA8–RB interaction is required for timely entry of meiosis in mouse female germ cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Xi Li & Alfonso Poire & Kang Jin Jeong & Dong Zhang & Tugba Yildiran Ozmen & Gang Chen & Chaoyang Sun & Gordon B. Mills, 2024. "C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    14. Xiaojun Ren & Jianqing Liang & Yiming Zhang & Ning Jiang & Yuhui Xu & Mengdi Qiu & Yiqin Wang & Bing Zhao & Xiaojun Chen, 2022. "Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Gaofei Li & Yicong Sun & Immanuel Kwok & Liting Yang & Wanying Wen & Peixian Huang & Mei Wu & Jing Li & Zhibin Huang & Zhaoyuan Liu & Shuai He & Wan Peng & Jin-Xin Bei & Florent Ginhoux & Lai Guan Ng , 2024. "Cebp1 and Cebpβ transcriptional axis controls eosinophilopoiesis in zebrafish," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    16. Adele M. Alchahin & Shenglin Mei & Ioanna Tsea & Taghreed Hirz & Youmna Kfoury & Douglas Dahl & Chin-Lee Wu & Alexander O. Subtelny & Shulin Wu & David T. Scadden & John H. Shin & Philip J. Saylor & D, 2022. "A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Anneke Brümmer & Sven Bergmann, 2024. "Disentangling genetic effects on transcriptional and post-transcriptional gene regulation through integrating exon and intron expression QTLs," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Liang Yong & Yafen Yu & Bao Li & Huiyao Ge & Qi Zhen & Yiwen Mao & Yanxia Yu & Lu Cao & Ruixue Zhang & Zhuo Li & Yirui Wang & Wencheng Fan & Chang Zhang & Daiyue Wang & Sihan Luo & Yuanming Bai & Shir, 2022. "Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Bibiana Costa & Jennifer Becker & Tobias Krammer & Felix Mulenge & Verónica Durán & Andreas Pavlou & Olivia Luise Gern & Xiaojing Chu & Yang Li & Luka Čičin-Šain & Britta Eiz-Vesper & Martin Messerle , 2024. "Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    20. Min Zhang & Aleksandra Bzura & Essa Y. Baitei & Zisen Zhou & Jake B. Spicer & Charlotte Poile & Jan Rogel & Amy Branson & Amy King & Shaun Barber & Tamihiro Kamata & Joanna Dzialo & James Harber & Ala, 2024. "A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma," Nature Communications, Nature, vol. 15(1), pages 1-14, 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:14:y:2023:i:1:d:10.1038_s41467-022-35701-8. 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.