2. Academic Validation
  3. Neutrophil extracellular traps promote angiogenesis in gastric cancer

Neutrophil extracellular traps promote angiogenesis in gastric cancer

  • Cell Commun Signal. 2023 Jul 21;21(1):176. doi: 10.1186/s12964-023-01196-z.
Shifeng Yang # 1 2,  Boshi Sun # 1,  Jiacheng Li 3,  Nana Li 1,  Ange Zhang 1,  Xinyu Zhang 4,  Hao Yang 5,  Xiaoming Zou 6
Affiliations

Affiliations

  • 1 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang DistrictHeilongjiang Province, Harbin, 150001, China.
  • 2 The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, China.
  • 3 Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Heilongjiang Province, Jiamusi, 154002, China.
  • 4 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang DistrictHeilongjiang Province, Harbin, 150001, China. [email protected].
  • 5 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang DistrictHeilongjiang Province, Harbin, 150001, China. [email protected].
  • 6 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang DistrictHeilongjiang Province, Harbin, 150001, China. [email protected].
  • # Contributed equally.
PMID: 37480055 DOI: 10.1186/s12964-023-01196-z
Abstract

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.

Keywords

Angiogenesis; CCDC25; Gastric cancer; Neutrophil extracellular traps; Proteomic techniques.

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