IntracellularPorphyromonas gingivalisPromotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells

Porphyromonas gingivalisis a member of the dysbiotic oral microbiome associated with oral inflammation and periodontal disease. Intriguingly, epidemiological studies linkP. gingivalisto 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 ofP. gingivalisin pancreatic tumorigenesis using cell lines and a xenograft model. LiveP. gingivalisinduced 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 toP. gingivalison other cancer and immune cells, and is required forP. gingivalisto induce alveolar bone resorption. Instead, we found thatP. gingivalissurvives 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 withP. gingivalisled to enhanced growth in vivo. To the best of our knowledge, this study is the first to demonstrate the direct effect of exposure toP. gingivalison the tumorigenic behavior of pancreatic cancer cell lines. Our findings shed light on potential mechanisms underlying the pancreatic cancer-periodontitis link.