Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model

Abstract

Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.

Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results from the Women's Health Initiative Observational Cohort

“…As such, they may become cocooned within these M 2 macrophages and persist long enough within the circulatory system to reach distant organs and produce adverse effects. Scientific reports also show Porphyromonas gingivalis and Fusobacterium nucleatum can promote tumor progression by activating toll-like receptors (TLRs) on oral epithelial cells to upregulate the IL-6/STAT3 pathway (41). TLR activation has been linked to inflammation, cellular proliferation, invasion, and evasion of anti-tumoral immune responses, (42,43) and increased expression of TLR-5 has been observed in oral cancers (44,45).…”

Gut microbiome of Moroccan colorectal cancer patients

“…An association between oral bacteria, periodontal disease, and cancer has been established, specifically between Porphyromonas gingivalis and F. nucleatum [99, 103–106]. Porphyromonas has been associated with oral periodontal disease.…”

Role of Porphyromonas gingivalis in oral squamous cell carcinoma development: A systematic review

“…Studies were classified into three main groups according to oral specimen origins. In the first one, three studies (18.75%) used epithelial cells from human samples (Table ); in the second, three studies (18.75%) evaluated murine models (Table ); and in the last one, 11 studies (62.5%) were developed in pre‐established cell lines (Table ).…”