|Table of Contents|

Analysis of neutrophil heterogeneity in orthotopic mouse models of hepatocellular carcinoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 23
Page:
4425-4431
Research Field:
Publishing date:

Info

Title:
Analysis of neutrophil heterogeneity in orthotopic mouse models of hepatocellular carcinoma
Author(s):
HE Gaixia1; FENG Jun1; ZHOU Ying1; LI Wenjuan1; LIANG Yingxue1; SHANG Qi1; ZHANG Xurui1; LI Zongfang1; 2
1.National-Local Joint Engineering Research Center of Biodiagnostics and Biotherapy,Second Affiliated Hospital of Xi’an Jiaotong University,Shaanxi Xi’an 710004,China;2.Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases,Shaanxi Xi’an 710004,China.
Keywords:
neutrophil; tumor-associated neutrophils; heterogeneity; hepatocellular carcinoma; orthotopic mouse model
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2024.23.002
Abstract:
Objective:To investigate the heterogeneity of neutrophils in bone marrow,peripheral blood,spleen,and liver of mouse model with orthotopic hepatocellular carcinoma(HCC).Methods:Sixteen healthy female BALB/c mice,aged at 6~8 weeks,were randomly divided into the orthotopic tumor-bearing group and control group.The tumor model was established by orthotopically injection of H22 cell line into the liver,while the control group received PBS injection as a sham surgery control.At 18~20 days post-inoculation,bone marrow,spleen,and liver tissues were collected from both groups of mice.Immune cells were isolated,and the proportion of neutrophils was detected by flow cytometry.The heterogeneity of neutrophilsubsets in HCC-bearing mice was examined based on the expression of CXCR2 and CD101 molecules.Results:Compared to the control group,the proportion of neutrophils significantly increased in the bone marrow(BM),peripheral blood,spleen,and liver of tumor-bearing mice.Further analysis revealed the coexistence of neutrophil subpopulations at different stages of maturation within these organs in HCC mice,including CXCR2-CD101+,CXCR2+CD101+,CXCR2+CD101-,and CXCR2-CD101- subpopulations,supporting the heterogeneity of neutrophils.Specifically,in the BM of HCC mice,there was a marked elevation in the proportions of the CXCR2-CD101+ subset and the CXCR2-CD101- immature subset,while the CXCR2+CD101+ mature subset and the CXCR2+CD101- low maturity subset decrease significantly.A similar pattern was observed in the spleen and liver of tumor mice,with increased proportions of the CXCR2-CD101+ subset,the CXCR2+CD101- low maturity subset,the CXCR2-CD101- immature subset,and decreased proportion of mature CXCR2+CD101+ neutrophils,indicating an overall shift towards an increase in immature or less mature neutrophils and a decrease in mature neutrophils in peripheral organs.Conclusion:This study demonstrates a significant elevation in the number of neutrophils and notable alterations in the proportion of their subpopulations in the bone marrow,spleen,and liver of HCC mice during liver cancer progression.These findings provide valuable insights into the phenotypic heterogeneity of neutrophils in liver cancer progression and offer a novel perspective for further elucidating the mechanisms underlying neutrophil involvement in liver cancer.

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Memo

Memo:
National Natural Science Foundation of China(No.81802455);国家自然科学基金（编号：81802455）；陕西省自然科学基础研究计划项目（编号：2019JQ-962）；西安交大基础临床融合项目（编号：YXJLRH2022098）；西安交大二附院自由探索项目［编号：2020YJ(ZYTS)546-03］
Last Update: 2024-11-01