Abstract 132: Direct interactions of oral bacteria and oral squamous cell carcinoma cells

Abstract

Abstract Head and neck cancers (HNC) are the sixth most common cancer worldwide with more than 90% being squamous cell carcinoma. HNC can occur in the oral cavity, oropharynx, larynx or hypopharynx, or nasal cavities. Oral squamous cell carcinoma (OSCC) 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 vital 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 (Streptococcus mutans, Enterococcus faecalis, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans) and non-pathogenic (Streptococcus parasanguinis) bacteria. OSCC cells (A253, Cal27, FaDu, SCC-4, SCC- 9, SCC-25, SCC-152) were assessed for changes in cell proliferation, gene expression, and capacity to invade. Results: Pathogenic oral bacteria increased proliferation in A253 OSCC cells. Enterococcus faecalis increased proliferation of SCC-4, SCC-25 and SCC-152 cells. No increase in proliferation was seen in FaDu and Cal27 cells. When examining changes in gene expression, oral bacteria increased MMP2 expression in A253 cells.Enterococcus faecalis increased JAG1, markers of hedgehog signaling (GLI1, GLI2), cell proliferation (CCDN1, CDKN1A), and cell invasion (MMP2) in SCC-4. In SCC-25 cells, Enterococcus faecalis increased JAG1, GLI1, and GLI2. Despite having no effect in total proliferation, Enterococcus faecalis increased HES1 (a marker of Notch activity), GLI1, and GLI2 in Cal27 cells. In SCC-9 cells, GLI1 expression was increased with all treatments. Streptococcus mutans increased MMP9 and HES1. Aggregatibacter actinomycetemcomitans increased MMP2 and MMP9. Enterococcus faecalis and Fusobacterium nucleatum also increased HES1. Conclusions: Both the chemical and spatial interactions between OSCC and oral bacterium may play a role in tumor progression and migration by regulating proliferation of cancer cells and cellular signaling. A direct infection model, as opposed to interactions with bacterial spent media, showed more potential in terms of affecting cell viability and likely gene regulation as well. Future experiments will further explore the interactions, including the complexity of the oral biofilm in cancer patients and the presence of multiple bacteria. Citation Format: Stefan Kovac, Tiara Napier, Jessica Scoffield, Hope Amm. Direct interactions of oral bacteria and oral squamous cell carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 132.