Fusobacteria modulate oral carcinogenesis and promote cancer progression

ABSTRACT

Background: Evidence suggest periodontal bacterial infection can contribute to oral cancer initiation and progression.

Aim: To investigate the effects of periodontal bacteria on oral cancer cell behavior using a cell-based system and a mouse carcinogenesis model.

Methods: Oral cancer cell lines were polyinfected with four periodontal bacteria. Cytokine levels and relative changes in oncogene mRNA expression were determined post-infection. Oral tumours in mice induced by 4-nitroquinoline-1-oxide (4NQO) were compared with and without administrating periodontal bacteria.

Results: Polyinfected oral cancer cells had upregulated MMP1, MMP9, and IL-8. The expression of cell survival markers MYC, JAK1, and STAT3 and epithelial-mesenchymal transition markers ZEB1 and TGF-β were also significantly elevated. Monoinfections showed F. nucleatum alone had comparable or greater effects than the four bacteria together. Fusobacterial culture supernatant, primarily LPS, was sufficient to induce IL-8 secretion, demonstrating that direct contact of live Fusobacteria with cancer cells might not be required to exert changes in cancer cell behaviour. In the 4NQO-induced oral tumour model, mice infected with bacteria developed significantly larger and more numerous lesions compared to those not infected.

Conclusion: This study demonstrated that Fusobacteria could potentially enhance cancer cell invasiveness, survival, and EMT when presented in the oral tumour microenvironment.

Abbreviations: 4NQO, 4-nitroquinoline-1-oxide; ELISA, enzyme-linked immunosorbent assay; EMT, epithelial–mesenchymal transition; IL-8, interleukin-8; JAK1, Janus kinase 1; LPS, lipopolysaccharide; MMP, matrix metalloproteinase; OSCCs, oral squamous cell carcinomas; PK, proteinase K; PMB, Polymyxin B; qRT-PCR, quantitative real-time polymerase chain reaction; STAT3, signal transducer and activator of transcription 3; TGF-β, transforming growth factor beta; ZEB1, zinc finger E-Box binding homeobox 1

KEYWORDS:

• 4NQO
• oral cancer
• periodontal bacteria
• inflammation
• fusobacterium nucleatum

Acknowledgements

This research was supported in part by the Andrew J. Semesco Foundation, Ocala, FL. We are also grateful for UMM ALQURA University, Saudi Arabia and Saudi Arabian Cultural Mission to the U.S. for their financial support.

Disclosure statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Andrew J. Semesco Foundation [N/A]; Saudi Arabian Cultural Mission to the U.S. [N/A].