F. nucleatum Signaling Proliferates Pancreatic Cancer Cells

Tumor-associated microbiomes have been known to influence tumor development and progression, but the precise mechanisms behind these patterns remain unclear. Researchers from Virginia Tech’s Department of Biomedical Engineering and Mechanics and the Department of Biochemistry published work in Science Signaling detailing how a common oral bacterium plays a role in cancer’s growth and movement throughout the body.

“The tumor microbiome can affect the progression of cancer, so our goal is to better understand the role of these bacteria in cancer,” says first author Barath Udayasuryan, Ph.D., alumnus from the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. “Only in early 2022 was the tumor microbiome patently recognized as a hallmark of cancer. Cancer biology and infection biology were usually considered disparate fields of study, but recent merging of the two fields is revealing fundamental insights into cancer progression. Our focus is at the forefront of this emerging paradigm, and we are on the cutting edge of research, looking at things no one has before.”

Fusobacterium nucleatum, the bacterium of choice for this study, is a common oral microbe studied in relation to mouth diseases, such as periodontitis and gingivitis, as well colorectal cancer cell migration. Previous studies have identified this bacterium’s presence in pancreatic cancer, leading the Virginia Tech team to wonder if this microbe also plays a role in activating tumor migration within the pancreas.

The team noticed that it was challenging to quantify the number of migrated pancreatic cancer cells, as the total seemed to drastically outnumber the cell populations they expected to observe. For further exploration, the scientists used in vitro tumor-on-a-chip models to confirm that this microbe binds and invades pancreatic cancer cells before then secreting molecules that stimulate the growth of cancerous cells. These findings explain why the team observed so many more cells in their experiments than expected, as well as identify an increase in the migration of infected cells.

Additionally, the researchers found that this microbe can infect non-tumorous pancreatic tissue cells to grow and spread more rapidly. These new insights reveal that any cell could be potentially more susceptible to cancerous growth or metastasis, depending on the surrounding environment.

The team hopes that these findings provide researchers with a more comprehensive view of how microbiomes impact tumor growth and progression, as well as new ideas for chemotherapies and immunotherapies.

“While we have shown that F. nucleatum is capable of driving pancreatic cancer cell proliferation and migration, we do not yet know to what extent these outcomes translate to living systems or human patients,” says senior author Scott Verbridge, associate professor in biomedical engineering and mechanics at Virginia Tech. “These next steps will be important future work, which could ultimately teach us whether or not this knowledge could lead to more effective therapies that are tailored to a patient’s own microbiome components.”