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Open AccessArticle

Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells

1
The Institute of Dental Sciences, Hebrew University, Hadassah Faculty of Dental Medicine, Jerusalem 9112102, Israel
2
Sharett Oncology Institute, Hadassah-Hebrew University Medical Center, Jerusalem 9112102, Israel
*
Authors to whom correspondence should be addressed.
Equal contribution (these authors share the senior authorship).
Cancers 2020, 12(8), 2331; https://doi.org/10.3390/cancers12082331
Received: 2 July 2020 / Revised: 10 August 2020 / Accepted: 14 August 2020 / Published: 18 August 2020
(This article belongs to the Special Issue Recent Advances in Pancreatic Ductal Adenocarcinoma)
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. View Full-Text
Keywords: Porphyromonas gingivalis; periodontitis; pancreatic neoplasms; tumor hypoxia; carcinogenesis Porphyromonas gingivalis; periodontitis; pancreatic neoplasms; tumor hypoxia; carcinogenesis
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MDPI and ACS Style

Gnanasekaran, J.; Binder Gallimidi, A.; Saba, E.; Pandi, K.; Eli Berchoer, L.; Hermano, E.; Angabo, S.; Makkawi, H.; Khashan, A.; Daoud, A.; Elkin, M.; Nussbaum, G. Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells. Cancers 2020, 12, 2331. https://doi.org/10.3390/cancers12082331

AMA Style

Gnanasekaran J, Binder Gallimidi A, Saba E, Pandi K, Eli Berchoer L, Hermano E, Angabo S, Makkawi H, Khashan A, Daoud A, Elkin M, Nussbaum G. Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells. Cancers. 2020; 12(8):2331. https://doi.org/10.3390/cancers12082331

Chicago/Turabian Style

Gnanasekaran, JebaMercy; Binder Gallimidi, Adi; Saba, Elias; Pandi, Karthikeyan; Eli Berchoer, Luba; Hermano, Esther; Angabo, Sarah; Makkawi, Hasna′a; Khashan, Arin; Daoud, Alaa; Elkin, Michael; Nussbaum, Gabriel. 2020. "Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells" Cancers 12, no. 8: 2331. https://doi.org/10.3390/cancers12082331

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