Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3
| Autor: | Weiguo Hu, Yongjing Chen, Jingting Jiang, Ying Wang, Shanfen Jia, Shenghua Zhan, Ping-Jin Gao, Lijuan Cao, Yanan Li, Yufang Shi, Changshun Shao, Min Tao, Zhiyuan Zheng, Mengting Zhu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer microenvironment
Lung Neoplasms Neutrophils Science General Physics and Astronomy Mice Nude Breast Neoplasms Extracellular Traps General Biochemistry Genetics and Molecular Biology Article Metastasis Mice Breast cancer Th2 Cells Downregulation and upregulation Cell Line Tumor Tumor Microenvironment Medicine Animals Humans Neoplasm Metastasis Lung Multidisciplinary biology business.industry Mesenchymal stem cell Mesenchymal Stem Cells General Chemistry Neutrophil extracellular traps Complement C3 respiratory system medicine.disease medicine.anatomical_structure Neutrophil Infiltration Cancer cell biology.protein Cancer research Tumour immunology Cytokines Female Antibody business STAT6 Transcription Factor Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
| ISSN: | 2041-1723 |
| Popis: | 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. The formation of the pre-metastatic niche enables the colonisation of disseminated cancer cells in distant organs. Here, the authors show that Th2 cytokines induce Complement 3 production in lung mesenchymal stromal cells, which recruits neutrophils and promotes the formation neutrophil extracellular traps, facilitating breast cancer cell metastasis to the lungs. |
| Databáze: | OpenAIRE |
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