Abstract

Abstract Periodontitis is a chronic infectious disease characterized by inflammation and destruction of periodontal tissues including the periodontal ligament fibers and alveolar bone. Recent epidemiological studies have revealed a significant association between periodontitis and oral cancer. While the precise mechanisms that mediate these associations are not well understood, periodontal pathogens, including Treponema denticola (T. denticola), which are believed to initiate the destructive inflammatory responses and dysbiosis or dysregulation of tissue homeostasis that characterize periodontal disease may contribute to oral cancer. However, knowledge about T. denticola's contribution to oral cancer is limited. Previously, we showed that nisin ZP, a bacteriocin and commonly used food preservative, reduced tumorigenesis in vivo and long term treatment with nisin ZP extended survival. In a separate study, we further showed that nisin ZP exhibits antimicrobial and antibiofilm effects, limiting T. denticola viability. The antimicrobial doses of nisin ZP are two orders of magnitude lower than the antitumor doses. The present study investigated the impact of T. denticola on the stemness, migration, and tumorigenesis of oral squamous cell carcinoma (OSCC), and nisin's potential modulatory effects on these processes. To investigate the role of T. denticola on OSCC tumorigenesis, OSCC cells were treated with T. denticola and with or without nisin ZP then assayed for stemness (orasphere) and migration. Treatment with T. denticola enhanced OSCC orasphere formation and migration without affecting cell viability or inducing apoptosis. Addition of nisin ZP inhibited these T. denticola-mediated processes. These data indicate that the periodontal pathogen T. denticola promotes stemness and migration of OSCC cells, and thereby may contribute to oral cancer tumorigenesis. Citation Format: Pachiyappan Kamarajan, Islam Ateia, Jae M. Shin, J Christopher Fenno, Yvonne L. Kapila. Treponema denticola, a periodontal pathogen, promotes stemness and migration in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3294.

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