Abstract
Oral squamous cell carcinoma (OSCC) is an aggressive head and neck cancer. Evidence showed that some pathogenic bacteria are associated with periodontitis and oral cancer. The change in oral microbiome composition and the role of the specific periodontal pathogen Streptococcus mutans in OSCC were investigated. We analyzed the microbiome of oral biofilms to identify if the oral microbiome composition was associated with OSCC. The role of S. mutans with clinical prognosis for OSCC was also examined. We further examined the role of S. mutans infection in OSCC progression in preclinical experiments. The microbiome assay by oral biofilms revealed that there was different microbiota composition between OSCC patients and health participants. Furthermore, the microbiota profiles showed that S. mutans abundance was associated with the development of OSCC development. Using the 16S rRNA PCR analysis, the presence of S. mutans was associated with advanced clinical stage and poor disease control. Furthermore, in the 4-nitroquinoline 1-oxide-induced mouse model, the presence of S. mutans was associated with elevated invasive oral cancer incidence. By cellular and xenograft tumor model using oral cancer cells, S. mutans infection was associated with the increased tumor aggressiveness, the epithelial-mesenchymal transition and interleukin-6 (IL-6) production; it also correlated with the recruitment of myeloid-derived-suppressor cells. When IL-6 signaling inhibited, the effects of S. mutans on tumor aggressiveness were attenuated. In conclusion, S. mutans may have the additive effect on oral cancer development and progression. Good oral hygiene to eradicate S. mutans or targeting IL-6 signaling could be a promising strategy for OSCC associated with S.mutans infection.