TY - JOUR
T1 - Intracellular Porphyromonas gingivalis promotes the tumorigenic behavior of pancreatic carcinoma cells
AU - Gnanasekaran, Jebamercy
AU - Gallimidi, Adi Binder
AU - Saba, Elias
AU - Pandi, Karthikeyan
AU - Berchoer, Luba Eli
AU - Hermano, Esther
AU - Angabo, Sarah
AU - Makkawi, Hasna′a
AU - Khashan, Arin
AU - Daoud, Alaa
AU - Elkin, Michael
AU - Nussbaum, Gabriel
N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Carcinogenesis
KW - Pancreatic neoplasms
KW - Periodontitis
KW - Porphyromonas gingivalis
KW - Tumor hypoxia
UR - http://www.scopus.com/inward/record.url?scp=85090534422&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers12082331
DO - https://doi.org/10.3390/cancers12082331
M3 - مقالة
SN - 2072-6694
VL - 12
SP - 1
EP - 14
JO - Cancers
JF - Cancers
IS - 8
M1 - 2331
ER -