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

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 Morii, Noriaki Emoto, Yasushi Shintani and Masaru Ishii ()
Additional contact information
Seiji Taniguchi: Osaka University Graduate School of Medicine
Takahiro Matsui: 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
Yutaka Uchida: Osaka University Graduate School of Medicine
Takao Sudo: Osaka University Graduate School of Medicine
Junichi Kikuta: Osaka University Graduate School of Medicine
Tetsuya Hara: Kobe Pharmaceutical University
Daisuke Motooka: Research Institute for Microbial Diseases, Osaka University
Yu-Chen Liu: WPI-Immunology Frontier Research Center, Osaka University
Daisuke Okuzaki: Research Institute for Microbial Diseases, 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

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35701-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35701-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-35701-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().