Bacteria that colonize tumors may contribute to cancer progression and metastasis, suggests new research from the Fred Hutchinson Cancer Center.
The oral bacterium Fusobacterium nucleatum, a component of dental plaque, is known to be present in oral and colorectal tumors. Two studies published this week took a closer look at how F. nucleatum and other microbes affect such tumors.
Using microscopy and techniques to measure proteins and RNA, researchers found that F. nucleatum and other bacteria populate areas of tumors that show immune system suppression. Bacteria-infected tumor cells also had alterations in molecular pathways involved in cell migration and metastasis, among other processes.
To see if the bacteria had a direct effect on tumors, the researchers infected clusters of colerectal tumor cells in a petri dish with F. nucleatum. They found that infected clusters attracted a type of cell which may be involved in immunosuppression. Infected cells were also more likely to migrate outside of the cluster.
The study, published in Nature, suggests that bacteria may foster cancer progression by promoting metastasis and creating an environment that resists tumor 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.
The findings are also consistent with previous studies showing that F. nucleatum is associated with tumor progression and poorer patient outcomes in patients with colorectal cancer. They also suggest that measures to control bacteria could potentially have a role in cancer treatment.
Because broad spectrum antibiotics kill beneficial bacteria, the researchers looked for compounds that specifically inhibit F. nucleatum.
In a second study in Cell Reports, they showed that a common chemotherapy drug, 5-fluorouracil, is also a potent inhibitor of the microbe. Other types of bacteria in colorectal tumors could also metabolize 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 Fred Hutch assistant professor Christopher Johnston in a Fred Hutch post on the new studies. Johnston led the research along with Fred Hutch assistant professor Susan Bullman.
The new studies may be relevant for other types of cancer.
Until a few years ago, tumors were thought to be sterile. But more recently bacteria have been detected in a variety of tumor types.