Neutrophil-derived reactive oxygen species promote tumor colonization
| Autor: | Rikard Holmdahl, Jianghong Zhong, Huqiao Luo, Qijing Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell type Neutrophils QH301-705.5 Transgene Interleukin-1beta Mutant Medicine (miscellaneous) Mice Transgenic Polymorphism Single Nucleotide Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms Animals Humans Calgranulin A Biology (General) Melanoma Lung Mice Knockout chemistry.chemical_classification Reactive oxygen species biology Disease genetics Macrophages Wild type NADPH Oxidases Neutrophil cytosolic factor 1 Gene Expression Regulation Neoplastic Mice Inbred C57BL 030104 developmental biology chemistry Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein cardiovascular system Antibody Reactive Oxygen Species General Agricultural and Biological Sciences |
| Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-7 (2021) Communications Biology |
| ISSN: | 2399-3642 |
| Popis: | A single-nucleotide polymorphism of neutrophil cytosolic factor 1 (Ncf1), leading to an impaired generation of reactive oxygen species (ROS), is a causative genetic factor for autoimmune disease. To study a possible tumor protection effect by the Ncf1 mutation in a manner dependent on cell types, we used experimental mouse models of lung colonization assay by B16F10 melanoma cells. We observed fewer tumor foci in Ncf1 mutant mice, irrespective of αβT, γδT, B-cell deficiencies, or of a functional Ncf1 expression in CD68-positive monocytes/macrophages. The susceptibility to tumor colonization was restored by the human S100A8 (MRP8) promoter directing a functional Ncf1 expression to granulocytes. This effect was associated with an increase of both ROS and interleukin 1 beta (IL-1β) production from lung neutrophils. Moreover, neutrophil depletion by anti-Ly6G antibodies increased tumor colonization in wild type but failed in the Ncf1 mutant mice. In conclusion, tumor colonization is counteracted by ROS-activated and IL-1β-secreting tissue neutrophils. Zhong et al. investigate how mutations in the NOX2 subunit Ncf1 lead to reduced ROS formation and affect B16F10 lung metastasis. The study highlights neutrophils as key to detrimental ROS-formation and suggest the involvement of IL-1 beta and RAGE. |
| Databáze: | OpenAIRE |
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