Oral squamous cell carcinoma (OSCC) is one of the prevalent cancers worldwide, and oral microbiota dysbiosis is considered a risk factor for causing OSCC. It was reported that the abundance of Prevotella intermedia was increased in the saliva samples of OSCC patients compared to healthy controls. The relation between P. intermedia and OSCC still needed to be clarified. Therefore, we hypothesized that P. intermedia plays a crucial role in OSCC development. In the cell culture assays, including trans-well and wound-healing assays, of SG, SCC-15, and SAS cells, P. intermedia ATCC 25611 and its conditioned medium enhanced cell proliferation and migration, and this activity was higher than in clinical strains. The activity has been linked to P. intermedia interpain A, a cysteine protease, and cellular protease-activated receptor 2 (PAR-2) with proteomic analysis, the cell culture assays with protease inhibiter E64 and PAR-2 antagonist FSLLRY-NH2. In the AOM/DSS colorectal cancer mouse model, the P. intermedia ATCC 25611 was also demonstrated to increase colon tumor number. In conclusion, P. intermedia protease InpA may affect human cancer cells.
