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Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells

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 b...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465784/
https://www.ncbi.nlm.nih.gov/pubmed/32824786
http://dx.doi.org/10.3390/cancers12082331
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author 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
author_facet 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
author_sort Gnanasekaran, JebaMercy
collection PubMed
description 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.
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spelling pubmed-74657842020-09-04 Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells 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 Cancers (Basel) Article 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. MDPI 2020-08-18 /pmc/articles/PMC7465784/ /pubmed/32824786 http://dx.doi.org/10.3390/cancers12082331 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells
title Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells
title_full Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells
title_fullStr Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells
title_full_unstemmed Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells
title_short Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells
title_sort intracellular porphyromonas gingivalis promotes the tumorigenic behavior of pancreatic carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465784/
https://www.ncbi.nlm.nih.gov/pubmed/32824786
http://dx.doi.org/10.3390/cancers12082331
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