Neutrophil extracellular traps promote angiogenesis in gastric cancer

Although antiangiogenic therapy has been used in gastric cancer, disease progression due to drug resistance remains common. Neutrophils play an important role in the occurrence and progression of cancer via neutrophil extracellular traps (NETs). However, few studies have investigated angiogenic regu...

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Bibliographic Details
Published in:Cell communication and signaling 2023-07, Vol.21 (1), p.176-176, Article 176
Main Authors: Yang, Shifeng, Sun, Boshi, Li, Jiacheng, Li, Nana, Zhang, Ange, Zhang, Xinyu, Yang, Hao, Zou, Xiaoming
Format: Article
Language:English
Subjects:
Alcohol
Angiogenesis
Animals
Aorta
Biological Assay
Cancer therapies
CCDC25
Cells
Chemotaxis
Disease Models, Animal
Drinking water
Drug resistance
Extracellular Traps
FDA approval
Gastric cancer
Leukocyte migration
Leukocytes (neutrophilic)
Medical prognosis
Metastasis
Mice
Neutrophil extracellular traps
Neutrophils
Peptides
Proteomic techniques
Proteomics
Rats
Spatial distribution
Stomach Neoplasms
Therapeutic targets
Tumors
Vascular endothelial growth factor
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Summary:Although antiangiogenic therapy has been used in gastric cancer, disease progression due to drug resistance remains common. Neutrophils play an important role in the occurrence and progression of cancer via neutrophil extracellular traps (NETs). However, few studies have investigated angiogenic regulation in gastric cancer. We aimed to determine the role of NETs in promoting angiogenesis in gastric cancer. Multiple immunohistochemical staining was used to analyze the spatial distribution of NETs and microvessels in patient tissue samples. A mouse subcutaneous tumor model was established to determine the effect of NETs on tumor growth, and changes in microvessel density were observed via immunohistochemical staining. We screened differentially expressed proteins in HUVECs stimulated by NETs via proteomics. Cell Counting Kit-8, EdU labeling, and tubule formation assays were used to verify the effect of NETs on HUVEC proliferation, migration, and tubule formation. Blocking NETs, which was related to decreased microvessel density, significantly inhibited tumor growth in the murine subcutaneous tumor model. Compared with those of the control group, tumor volume and mass among mice in the inhibition group decreased by 61.3% and 77.9%, respectively. The NET-DNA receptor CCDC25 was expressed in HUVECs, providing a platform for NETs to promote HUVEC proliferation, migration, and tubulation. In an in vitro rat aortic explant model, NETs induced HUVEC proliferation, survival, and chemotaxis, which were not significantly different from those observed in the VEGF stimulation group. Our results confirm that NETs promote angiogenesis in gastric cancer, providing a theoretical basis for identifying new anti-vascular therapeutic targets. Video Abstract.
ISSN:1478-811X
1478-811X
DOI:10.1186/s12964-023-01196-z