Fred Hutch research: Bacteria may make tumors more aggressive

Bacteria that colonize tumors may contribute to cancer progression, suggests new research from Fred Hutchinson Cancer Center.

The oral bacterium Fusobacterium nucleatum is found in dental plaque and also lurks in oral and colorectal tumors. Two studies published this week took a closer look at how F. nucleatum and other microbes affect such tumors.

Researchers found that F. nucleatum and other bacteria populate regions of the tumor that show immune system suppression. Tumor cells infected with bacteria also had alterations in molecules involved in cell migration and metastasis, among other processes.

Clusters of F. nucleatum-infected colorectal tumor cells in a petri dish attracted a type of cell which may mediate immunosuppression. Infected cells were also more likely to migrate outside of the cluster, akin to metastatic cells.

The study, published in Nature, suggests that bacteria may foster cancer progression by promoting metastasis and creating an environment that resists destruction by the immune system

The data “indicate a crucial role for intratumoral bacteria, reinforcing the need for more research in this area and demonstrating the technical feasibility of such work,” according to a separate commentary in the journal.

They findings also suggest that measures to control bacteria could potentially have a role in cancer treatment, according to a Fred Hutch post on the research, led by Fred Hutch assistant professors Christopher Johnston and Susan Bullman.

Bullman had previously shown that antibiotics can quell cancer in tests of infected human colorectal tumors engrafted onto mice. But the broad spectrum antibiotic used in the tests can also kill beneficial bacteria in the body.

In a second study in Cell Reports, the researchers looked for compounds that specifically inhibit F. nucleatum.

After testing 1,846 compounds, the researchers found to their surprise that some chemotherapy agents also inhibited F. nucleatum, including the commonly used drug 5-fluorouracil. Other types of bacteria in colorectal tumors broke down 5-fluorouracil, suggesting that they may contribute to chemotherapy resistance.

5-fluorouracil is known to quell cancer because it inhibits cell division. But the drug is also more effective against colorectal cancer than other tumor types, and that may be because of its ability to also kill Fusobacteria, speculated the researchers.

“The findings show that intratumoral microbes are not innocent bystanders during disease progression and suggest that the microbiota should be taken into consideration when thinking about optimal cancer treatments,” said Johnston in the post on the new studies.

The new findings are consistent with previous studies showing that F. nucleatum is associated with tumor progression and poorer patient outcomes in patients with colorectal cancer.

The findings also may be relevant for other types of cancer. Tumors were once thought to be sterile, but in recent years bacteria have been detected in a variety of tumor types.


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