Common oral bacteria can cause pancreatic cancer to metastasize

Virginia Tech researchers have identified features of a common oral bacterium that can metastasize to pancreatic cancer tumors, which may help guide future therapeutic interventions
.
This may play a key role
in cancer growth and aggressiveness in moving throughout the body.

Pancreatic cancer is the third leading cause
of cancer-related death in the United States.
A particularly aggressive pancreatic cancer, ductal adenocarcinoma, is expected to survive less than 6 months
.
Several features of the disease make it difficult to treat, including its ability to suppress the immune system, as well as its complex location and structure, which complicates
surgical and chemotherapy delivery.

Scott Verbridge and Barath Udayasuryan, PhDs, associate professors of biomedical engineering and mechanics, conducted research
on a type of bacteria found in pancreatic cancer and other types of tumors.
Most notably, they found the way
this bacterium may directly affect cancer progression and resistance to chemotherapy.
These results were presented Oct.
18 by Daniel J.
Slade, associate professor of biochemistry at Science Signaling, a leading expert in cancer microbes and their biochemical interactions with the tumor microenvironment, who also collaborates
with Verbridge and Udayasuryan.
Verbridge's Laboratory of Integrated Oncology has been working with Slade's team on cancer research
for years.
Together, they discovered the role of a specific microbe, F.
nucleatum, in pushing cancer cells to migrate, particularly in
colorectal cancer.

Since this microorganism is a common oral bacteria, it is often studied in relation
to oral diseases such as periodontitis and gingivitis.
But little
is known about how this microbe enters and adapts to the tumor microenvironment, thereby increasing the aggressiveness of cancer cell growth.
Other cancer studies have confirmed the microbe's presence in pancreatic cancer, leading Verbridge and his team to wonder if the bacteria might also activate tumor migration
in the pancreas.

"The tumor microbiome can influence cancer progression, so our goal is to better understand the role of these bacteria in cancer," Udayasuryan said
.
"It wasn't until early 2022 that the tumor microbiome was definitively identified as a marker
of cancer.
Cancer biology and infection biology are often thought of as separate fields of study, but the recent merger of the two has revealed fundamental insights
into cancer progression.
We're focused on the frontiers of this emerging paradigm, and we're at the forefront of research, looking at things
that have never been seen before.
”

When first analyzing the migration of infected pancreatic cancer cells, the researchers ran into an unexpected obstacle: They found that the number of migrating cells was difficult to quantify because the total number seemed to greatly exceed the number
of cells they expected to find in the system.
Using in vitro tumor microarray models, Verbridge and his team demonstrated that the microbe can bind and invade pancreatic cancer cells, then secrete molecules
that stimulate cancer cells to accelerate growth.
This finding explains why the team saw far
more cells in the experiment than expected.
This also allowed them to identify an increase in
migration of infected cells.

In another important finding, they found that the microbe can infect non-tumor-based normal pancreatic tissue cells
.
In their experiments, when a normal cell was infected, it continued to grow normally; However, its presence stimulates nearby cancer cells to grow and spread
faster.
The new findings expand current views
about non-cancerous cells in and around tumor cells and how cancer spreads so violently.
Any cell infected by this microbe may be more likely to become cancerous later in life, and even more prone to metastasis, which is why
most cancers end up killing their host.
With an understanding of how bacteria in tumors affect cancer growth and spread, scientists can design more effective chemotherapy or immunotherapies
.
These results also contribute to the development of diagnostic and prognostic tools to help detect cancer
early.

"We've proven that F.
Nucleatum is able to drive pancreatic cancer cells to proliferate and migrate, and we don't yet know to what extent these results translate to living systems or human patients," Verbridge said
.
"These next steps will be important work in the future, and can ultimately tell us whether this knowledge can lead to more effective treatments, tailored
to the patient's own microbial composition.
"

Verbridge said: "The host-microbiome interaction is complex because many bacterial residency actually supports human health and has been shown to improve the efficacy
of cancer treatment.
This makes my research very complex and meaningful, there are still many questions, and in the search for answers, we must carefully try to eliminate harmful bacteria that may have similarities
to their more beneficial relatives.
”