Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by stimulating the release of neutrophil extracellular traps in the tumor immune microenvironment.

IF 4.8 3区 医学 Q2 CELL BIOLOGY Inflammation Research Pub Date : 2024-05-01 Epub Date: 2023-12-27 DOI:10.1007/s00011-023-01822-z
Zhi-Chen Guo, Si-Li Jing, Xin-Yu Jia, Sadam Ahmed Elayah, Lin-Yang Xie, Hao Cui, Jun-Bo Tu, Si-Jia Na
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Abstract

Background: The aim of this study was to investigate the impact of Porphyromonas gingivalis (P. gingivalis) on the progression of oral squamous cell carcinoma (OSCC) through neutrophil extracellular traps (NETs) in the tumor immune microenvironment.

Methods: The expression of NETs-related markers was identified through immunohistochemistry, immunofluorescence, and Western blotting in different clinical stages of OSCC samples. The relationship between NETs-related markers and clinicopathological characteristics in 180 samples was analyzed using immunohistochemistry data. Furthermore, the ability to predict the prognosis of OSCC patients was determined by ROC curve analysis and survival analysis. The effect of P. gingivalis on the release of NETs was identified through immunofluorescence and immunohistochemistry, both in vitro and in vivo. CAL27 and SCC25 cell lines were subjected to NETs stimulation to elucidate the influence of NETs on various cellular processes, including cell proliferation, migration, invasion, and metastasis in vitro. Furthermore, the impact of NETs on the growth and metastatic potential of OSCC was assessed using in vivo models involving tumor-bearing mice and tumor metastasis mouse models.

Results: Immunochemistry analysis revealed a significant correlation between the NETs-related markers and clinical stage, living status as well as TN stage. P. gingivalis has demonstrated its ability to effectively induce the release of NETs both in vivo and in vitro. NETs have the potential to facilitate cell migration, invasion, and colony formation. Moreover, in vivo experiments have demonstrated that NETs play a pivotal role in promoting tumor metastasis.

Conclusion: High expression of NETs-related markers demonstrates a strong correlation with the progression of OSCC. Inhibition of the NETs release process stimulated by P. gingivalis and targeted NETs could potentially open up a novel avenue in the field of immunotherapy for patients afflicted with OSCC.

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牙龈卟啉单胞菌通过刺激肿瘤免疫微环境中中性粒细胞胞外捕获物的释放,促进口腔鳞状细胞癌的进展。
背景:本研究旨在探讨牙龈卟啉单胞菌(P. gingivalis)通过肿瘤免疫微环境中的中性粒细胞胞外陷阱(NETs)对口腔鳞状细胞癌(OSCC)进展的影响:方法:通过免疫组化、免疫荧光和 Western 印迹法鉴定不同临床分期 OSCC 样本中与 NETs 相关的标记物的表达。利用免疫组化数据分析了180份样本中NETs相关标记物与临床病理特征之间的关系。此外,还通过 ROC 曲线分析和生存分析确定了预测 OSCC 患者预后的能力。通过体外和体内免疫荧光和免疫组化鉴定了牙龈脓杆菌对 NETs 释放的影响。对 CAL27 和 SCC25 细胞系进行了 NETs 刺激,以阐明 NETs 对体外细胞增殖、迁移、侵袭和转移等各种细胞过程的影响。此外,还利用肿瘤小鼠体内模型和肿瘤转移小鼠模型评估了NETs对OSCC生长和转移潜力的影响:免疫化学分析表明,NETs相关标记物与临床分期、生存状态和TN分期之间存在显著相关性。牙龈脓疱病已证明它能在体内和体外有效诱导 NETs 的释放。NETs 具有促进细胞迁移、入侵和集落形成的潜力。此外,体内实验证明,NETs 在促进肿瘤转移方面发挥着关键作用:结论:NET 相关标记物的高表达与 OSCC 的进展密切相关。抑制牙龈脓胞刺激的 NETs 释放过程和靶向 NETs 有可能为 OSCC 患者的免疫疗法开辟一条新途径。
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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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