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Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3.
- Source :
-
Nature communications [Nat Commun] 2021 Oct 27; Vol. 12 (1), pp. 6202. Date of Electronic Publication: 2021 Oct 27. - Publication Year :
- 2021
-
Abstract
- Pre-metastatic niche formation is critical for the colonization of disseminated cancer cells in distant organs. Here we find that lung mesenchymal stromal cells (LMSCs) at pre-metastatic stage possess potent metastasis-promoting activity. RNA-seq reveals an upregulation of complement 3 (C3) in those LMSCs. C3 is found to promote neutrophil recruitment and the formation of neutrophil extracellular traps (NETs), which facilitate cancer cell metastasis to the lungs. C3 expression in LMSCs is induced and sustained by Th2 cytokines in a STAT6-dependent manner. LMSCs-driven lung metastasis is abolished in Th1-skewing Stat6-deficient mice. Blockade of IL-4 by antibody also attenuates LMSCs-driven cancer metastasis to the lungs. Consistently, metastasis is greatly enhanced in Th2-skewing T-bet-deficient mice or in nude mice adoptively transferred with T-bet-deficient T cells. Increased C3 levels are also detected in breast cancer patients. Our results suggest that targeting the Th2-STAT6-C3-NETs cascade may reduce breast cancer metastasis to the lungs.<br /> (© 2021. The Author(s).)
- Subjects :
- Animals
Breast Neoplasms immunology
Breast Neoplasms pathology
Cell Line, Tumor
Complement C3 metabolism
Extracellular Traps
Female
Humans
Lung immunology
Lung Neoplasms immunology
Lung Neoplasms secondary
Mesenchymal Stem Cells immunology
Mesenchymal Stem Cells metabolism
Mice
Mice, Nude
Neutrophil Infiltration
STAT6 Transcription Factor immunology
Signal Transduction
Tumor Microenvironment immunology
Complement C3 immunology
Cytokines immunology
Lung pathology
Mesenchymal Stem Cells pathology
Neoplasm Metastasis immunology
Neutrophils immunology
Th2 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 34707103
- Full Text :
- https://doi.org/10.1038/s41467-021-26460-z