Characterization of extracellular vesicles derived from pancreatic cancer cells infected with the oral bacterium Porphyromonas gingivalis

Pancreatic cancer (PCa) is one of the most aggressive cancers, and a leading cause of cancer-related death worldwide. Recently, many tumors, including PCa, were shown to harbor intracellular bacteria. Investigation into the roles of intratumor bacteria can contribute to a better understanding of PCa development. Porphyromonas gingivalis (Pg) is a gram-negative oral anaerobe closely linked to the progression of periodontitis, and considered a risk factor for several systemic diseases. Carriage of Pg in the oral cavity was linked to the risk of developing PCa in a prospective study, and we previously found that Pg promotes the growth of PCa cells in vitro and in vivo. However, it remains to be investigated whether Pg-infected PCa cells influence neighboring non-infected cells and the tumor microenvironment. Extracellular vesicles (EVs) are nano-sized lipid vesicles released from cells that contain various bioactive cargoes and play important roles in cell-cell communication. In the present study, we investigated whether EVs from Pg-infected PCa cells promote the proliferation and migration of non-infected PCa cells, and explored EV content such as miRNA and Pg-derived products. To profile miRNA patterns in EVs, we performed small RNA sequence analysis. We also studied the effect of Pg infection on metastatic potential of PCa cells and EV biogenesis and secretion. This study provides new insights into the mechanisms underlying the oncological effects of Pg on PCa, and may contribute to the design of novel strategies for the prevention and treatment of PCa.