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

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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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Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

Not applicable.

Funding

This work was supported by the Key Research and Development Projects of Shaanxi Province (2020SF-182).

Author information

Author notes

  1. Zhi-chen Guo, Si-li Jing, and Xin-yu Jia have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Shanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, 710004, China

    Zhi-chen Guo, Xin-yu Jia, Lin-yang Xie, Hao Cui, Jun-bo Tu & Si-jia Na

  2. Laboratory Center of Stomatology, College of Stomatology, Xi’an Jiaotong University, Xi’an, 710004, China

    Zhi-chen Guo, Xin-yu Jia, Lin-yang Xie, Hao Cui, Jun-bo Tu & Si-jia Na

  3. Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi’an Jiaotong University, Xi’an, 710004, China

    Zhi-chen Guo, Xin-yu Jia, Lin-yang Xie, Hao Cui, Jun-bo Tu & Si-jia Na

  4. Shannxi Eye Hospital, Xi’an People’s Hospital (Xi’an Fourth Hospital), Affiliated People’s Hospital of Northwest University, Xi’an, 710004, China

    Si-li Jing

  5. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Jiblah University for Medical and Health Sciences, Ibb, Yemen

    Sadam Ahmed Elayah

Authors
  1. Zhi-chen Guo
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Contributions

Zhi-chen Guo and Si-li Jing designed the research and performed the experiments; Xin-yu Jia and Sadam Ahmed Elayah contributed to the animal experiments. Lin-yang Xie and Hao Cui wrote the original draft; Jun-bo Tu and Si-jia Na designed the research, supervised the study, and revised the manuscript.

Corresponding authors

Correspondence to Jun-bo Tu or Si-jia Na.

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Conflict of interest

The authors declare that they have no conflicts of interest, financial or otherwise.

Ethical approval

Approval of the research protocol by an Institutional Reviewer Board: The research protocol was approved by the Ethics Committee of College of Stomatology, Xi'an Jiaotong University (xjkqll [2022] NO.028) and it conformed to the provisions of the Declaration of Helsinki. The informed consent was obtained from OSCC patients and healthy donors. Registry and the Registration No. of the study/trial: N/A.

Animal studies

All animal experiments were approved by the Animal Care and Use Committee of laboratory animal research center, Xi'an Jiaotong (XJTUAE2023-1317).

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Responsible Editor: John Di Battista.

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Guo, Zc., Jing, Sl., Jia, Xy. et al. Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by stimulating the release of neutrophil extracellular traps in the tumor immune microenvironment. Inflamm. Res. 73, 693–705 (2024). https://doi.org/10.1007/s00011-023-01822-z

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  • DOI: https://doi.org/10.1007/s00011-023-01822-z

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