Intracellular Porphyromonas gingivalis promotes the tumorigenic behavior of pancreatic carcinoma cells

Jebamercy Gnanasekaran, Adi Binder Gallimidi, Elias Saba, Karthikeyan Pandi, Luba Eli Berchoer, Esther Hermano, Sarah Angabo, Hasna′a Makkawi, Arin Khashan, Alaa Daoud, Michael Elkin*, Gabriel Nussbaum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Porphyromonas gingivalis is a member of the dysbiotic oral microbiome associated with oral inflammation and periodontal disease. Intriguingly, epidemiological studies link P. gingivalis to an increased risk of pancreatic cancer. Given that oral bacteria are detected in human pancreatic cancer, and both mouse and human pancreata harbor microbiota, we explored the involvement of P. gingivalis in pancreatic tumorigenesis using cell lines and a xenograft model. Live P. gingivalis induced proliferation of pancreatic cancer cells; however, surprisingly, this effect was independent of Toll-like receptor 2, the innate immune receptor that is engaged in response to P. gingivalis on other cancer and immune cells, and is required for P. gingivalis to induce alveolar bone resorption. Instead, we found that P. gingivalis survives inside pancreatic cancer cells, a trait that can be enhanced in vitro and is increased by hypoxia, a central characteristic of pancreatic cancer. Increased tumor cell proliferation was related to the degree of intracellular persistence, and infection of tumor cells with P. gingivalis led to enhanced growth in vivo. To the best of our knowledge, this study is the first to demonstrate the direct effect of exposure to P. gingivalis on the tumorigenic behavior of pancreatic cancer cell lines. Our findings shed light on potential mechanisms underlying the pancreatic cancer–periodontitis link.

Original languageAmerican English
Article number2331
Pages (from-to)1-14
Number of pages14
JournalCancers
Volume12
Issue number8
DOIs
StatePublished - Aug 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Carcinogenesis
  • Pancreatic neoplasms
  • Periodontitis
  • Porphyromonas gingivalis
  • Tumor hypoxia

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