Porphyromonas gingivalis suppresses oral squamous cell carcinoma progression by inhibiting MUC1 expression and remodeling the tumor microenvironment

• Published in: Molecular oncology 2024-05, Vol.18 (5), p.1174-1188
• Main Authors: Lan, Zhou, Zou, Ke‐Long, Cui, Hao, Zhao, Yu‐Yue, Yu, Guang‐Tao
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antitumor agents; Apoptosis; Bacteria; Bacterial Infection; bacterium therapy; Breast cancer; Cancer; Cancer Therapies; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - microbiology; Carcinoma, Squamous Cell - pathology; Cell Cycle; Cell death; Cell Line, Tumor; Cell Proliferation; Chemokines; Cytokines; Disease Progression; Female; Flow cytometry; Gene Expression Regulation, Neoplastic; Humans; Infectious diseases; Ligands; Lymphocytes; Male; Medical prognosis; Mice; Mice, Inbred BALB C; Mouth Neoplasms - metabolism; Mouth Neoplasms - microbiology; Mouth Neoplasms - pathology; Mucin; Mucin-1 - genetics; Mucin-1 - metabolism; Mucins; Oncology, Experimental; Oral cancer; Oral carcinoma; Oral cavity; Oral squamous cell carcinoma; Physiological aspects; Polysaccharides; Porphyromonas gingivalis; Signal transduction; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - microbiology; Squamous Cell Carcinoma of Head and Neck - pathology; Survival analysis; Transcriptomics; Tumor Microenvironment; Tumor suppression; Tumors
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1002/1878-0261.13517

Bacteria are the causative agents of various infectious diseases; however, the anti‐tumor effect of some bacterial species has attracted the attention of many scientists. The human oral cavity is inhabited by abundant and diverse bacterial communities and some of these bacterial communities could play a role in tumor suppression. Therefore, it is crucial to find oral bacterial species that show anti‐tumor activity on oral cancers. In the present study, we found that a high abundance of Porphyromonas gingivalis, an anaerobic periodontal pathogen, in the tumor microenvironment (TME) was positively associated with the longer survival of patients with oral squamous cell carcinoma (OSCC). An in vitro assay confirmed that P. gingivalis accelerated the death of OSCC cells by inducing cell cycle arrest at the G2/M phase, thus exerting its anti‐tumor effect. We also found that P. gingivalis significantly decreased tumor growth in a 4‐nitroquinoline‐1‐oxide‐induced in situ OSCC mouse model. The transcriptomics data demonstrated that P. gingivalis suppressed the biosynthesis of mucin O‐glycan and other O‐glycans, as well as the expression of chemokines. Validation experiments further confirmed the downregulation of mucin‐1 (MUC1) and C‐X‐C motif chemokine 17 (CXCL17) expression by P. gingivalis treatment. Flow cytometry analysis showed that P. gingivalis successfully reversed the immunosuppressive TME, thereby suppressing OSCC growth. In summary, the findings of the present study indicated that the rational use of P. gingivalis could serve as a promising therapeutic strategy for OSCC. The authors investigated the suppression of oral squamous cell carcinoma (OSCC) growth by Porphyromonas gingivalis. The bacterium downregulates MUC1 and CXCL17 expression, which contributes to the reversal of the immunosuppressive tumor microenvironment (TME), leading to OSCC growth inhibition.