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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362668/ https://www.ncbi.nlm.nih.gov/pubmed/37480055 http://dx.doi.org/10.1186/s12964-023-01196-z |
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author | Yang, Shifeng Sun, Boshi Li, Jiacheng Li, Nana Zhang, Ange Zhang, Xinyu Yang, Hao Zou, Xiaoming |
author_facet | Yang, Shifeng Sun, Boshi Li, Jiacheng Li, Nana Zhang, Ange Zhang, Xinyu Yang, Hao Zou, Xiaoming |
author_sort | Yang, Shifeng |
collection | PubMed |
description | 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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01196-z. |
format | Online Article Text |
id | pubmed-10362668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103626682023-07-23 Neutrophil extracellular traps promote angiogenesis in gastric cancer Yang, Shifeng Sun, Boshi Li, Jiacheng Li, Nana Zhang, Ange Zhang, Xinyu Yang, Hao Zou, Xiaoming Cell Commun Signal Research 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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01196-z. BioMed Central 2023-07-21 /pmc/articles/PMC10362668/ /pubmed/37480055 http://dx.doi.org/10.1186/s12964-023-01196-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Yang, Shifeng Sun, Boshi Li, Jiacheng Li, Nana Zhang, Ange Zhang, Xinyu Yang, Hao Zou, Xiaoming Neutrophil extracellular traps promote angiogenesis in gastric cancer |
title | Neutrophil extracellular traps promote angiogenesis in gastric cancer |
title_full | Neutrophil extracellular traps promote angiogenesis in gastric cancer |
title_fullStr | Neutrophil extracellular traps promote angiogenesis in gastric cancer |
title_full_unstemmed | Neutrophil extracellular traps promote angiogenesis in gastric cancer |
title_short | Neutrophil extracellular traps promote angiogenesis in gastric cancer |
title_sort | neutrophil extracellular traps promote angiogenesis in gastric cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362668/ https://www.ncbi.nlm.nih.gov/pubmed/37480055 http://dx.doi.org/10.1186/s12964-023-01196-z |
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