2. Academic Validation
  3. TREM1 facilitates the development of gastric cancer through regulating neutrophil extracellular traps-mediated macrophage polarization

TREM1 facilitates the development of gastric cancer through regulating neutrophil extracellular traps-mediated macrophage polarization

  • Dig Liver Dis. 2023 Dec 26:S1590-8658(23)01082-4. doi: 10.1016/j.dld.2023.12.002.
Cheng Yu 1,  Guoqiang Zhou 2,  Zhiliang Shi 2,  Liang Yu 2,  Xiaojun Zhou 3
Affiliations

Affiliations

  • 1 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China.
  • 2 Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China.
  • 3 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: [email protected].
PMID: 38151453 DOI: 10.1016/j.dld.2023.12.002
Abstract

Triggering receptor expressed on myeloid cell 1 (TREM1) elevation is associated with the unfavorable prognosis of gastric Cancer (GC) patients. This work uncovered the effects and mechanism of TREM1 in GC. IHC staining examined TREM1 expression in GC tissues. TREM1-knockout and TREM1 knock-in mice were generated prior to the construction of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GC mice model. H&E staining detected the pathological alternations of gastric tissues. IHC staining tested Ki67 expression. Wright-Giemsa staining performed neutrophil counting and flow cytometry analysis measured neutrophil infiltration. ELISA analyzed serum and tissue myeloperoxidase (MPO) levels and serum MPO-DNA levels. Immunofluorescence, Western blotting and related kits detected NETs formation. Immunofluorescence and IHC staining evaluated macrophage polarization. In MNNG-treated GES-1 cells and phorbal myristate acetate (PMA)-treated neutrophils, TREM1 expression was also examined. CCK-8 method and Western blotting assayed cell proliferation. Western blotting and immunofluorescence detected NETs formation. Flow cytometry analysis detected the changes of macrophage typing. TREM1 was overexpressed in tumor tissues, MNNG-treated GES-1 cells and PMA-treated neutrophils. TREM1 deficiency hindered tumor growth, reduced neutrophil infiltration, NETs formation and stimulated M1 macrophage polarization in MNNG-induced GC models. Neutrophil extracellular traps (NETs) degrader DNase-1 countervailed the impacts of TREM1 on MNNG-induced GC models in vivo. Collectively, TREM1 knockdown obstructed NETs-mediated M2 macrophage polarization to hamper GC progression.

Keywords

Gastric cancer; Macrophage polarization; Neutrophil extracellular traps; Neutrophil infiltration; TREM1.

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