Abstract

Abstract Oral squamous cell carcinoma (OSCC) is the most common site of head and neck squamous cell carcinoma. It is estimated to be diagnosed in 50,000 patients this year with an overall 5-year survival rate of 64%. The tumor microenvironment has been shown to play a role in the progression of many human cancers, including OSCC. Given the complexity of the oral microbiome, we hypothesize that OSCC and oral bacteria interact to affect the tumorigenic properties of OSCC. Methods: OSCC cells were cultured in the presence of oral pathogenic (Aggregatibacter actinomycetemcomitans (Aa), Enterococcus faecalis (Ef), Fusobacterium nucleatum (Fn)) and non-pathogenic (Streptococcus parasanguinis (Sp)) bacteria. Human oral keratinocytes (HOK) and OSCC cells were treated with oral bacteria and assessed for changes in cell proliferation and gene expression. Results: HOK treated with Ef demonstrated significantly increased proliferation and increased expression of HES1, MMP11, and CDKN1A(p21). Of the five OSCC cell lines, Ef increased proliferation in the two cell lines that were human papilloma virus positive (HPV+) (2A3, SCC152) and in one of three cell lines that were HPV negative (HPV-, Cal27). Ef increased the expression of HES1, MMP2, CDKN1A, and GLI1 in SCC152 cell and HES1, MMP11, and CDKN1A in 2A3 cells. Ef also increased the invasion of SCC152 cells in a transwell experiment. In HPV- Cal27 cells, Ef increased MMP2 and GLI1 expression. Aa also increased proliferation in 2A3 HPV+ cells. Fn did not increase proliferation of OSCC cells, but it did increase the expression of HES1, CDKN1A, and GLI1 in SCC152 HPV+ cells. Conclusions: Oral bacteria have direct interactions with human oral keratinocytes and cancer cells. In particular, Ef may be involved in both the initiation and progression stages of oral cancer. Citation Format: Stefan Kovac, Tiara S. Napier, Jessica Scoffield, Hope M. Amm. Oral bacteria effects on oral cancer initiation and progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2634.

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