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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
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