Virginia Tech researchers from the Departments of Biomedical Engineering and Mechanics and Biochemistry found a trait of a common oral bacterium that migrates to pancreatic cancer tumors that may guide future treatment. Fusobacterium nucleatum may help cancer spread aggressively.
Pancreatic cancer kills the third-most Americans with cancer. Pancreatic ductal adenocarcinoma has a six-month survival rate.
The disease’s immune suppression and unusual location and structure make surgery and treatment problematic.
Scott Verbridge, associate professor of biomedical engineering and mechanics, and Barath Udayasuryan Ph.D. ’22, an alumnus of the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, has studied a bacterium identified in pancreatic cancer tumors and others. Most importantly, they found ways the bacterium may directly affect cancer growth and drug resistance.
Science Signaling published these findings on October 18.
Verbridge and Udayasuryan worked with biochemistry associate professor Daniel J. Slade, a recognized expert on cancer microorganisms and their biochemical interactions with the tumor microenvironment.
Slade’s cancer research team has worked with Verbridge’s Laboratory of Integrative Tumor Ecology for years. They discovered that F. nucleatum drives colorectal cancer cell migration.
This ubiquitous oral bacterium has been researched in relation to mouth illnesses such as periodontitis and gingivitis. However, little was known about how the microorganism moves to and adapts to tumor microenvironments, boosting malignant growths. Verbridge and his team wondered if the microorganism, which was found in pancreatic cancer, was also stimulating tumor migration.
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The researchers encountered an unanticipated challenge while studying the migration of infected pancreatic cancer cells: the number of migratory cells looked to vastly surpass the predicted population of cells in the system. Verbridge and his team found using tumor-on-a-chip models that this bacterium can bind and penetrate pancreatic cancer cells, which subsequently release chemicals that increase cancer cell proliferation. This explains why the scientists saw more cells than predicted in their trials. Infected cells migrated more, too.
The microbe can infect non-tumorous pancreatic tissue cells, another important discovery. In their trials, infected normal cells grew normally, but neighboring cancer cells grew and spread faster.
This new knowledge increases our understanding of non-cancerous cells near tumorous cells and how cancer grows aggressively. Infected cells may be more likely to develop cancer or metastasize, which kills most cancer patients.
Scientists can improve chemotherapy and immunotherapy by understanding how tumor bacteria affect cancer growth. These findings may assist create cancer-detecting diagnostic and prognostic tools.
We have proven that F. nucleatum drives pancreatic cancer cell proliferation and migration, but we don’t know how this applies to living systems or patients. These following stages will determine if this knowledge may lead to more effective microbiome-tailored medicines.
Udayasuryan, B., et al. (2022) Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling. Science Signaling. doi.org/10.1126/scisignal.abn4948.