Evidence Shows Tumor Microbiota Promotes Metastasis

Bacteria inside tumors were found by researchers in China to promote cancer metastasis by strengthening host cells against mechanical stress in the bloodstream. The findings suggest such intracellular microbiota could be a potential target for preventing metastasis in broad cancer types at an early stage.

Microbes play a critical role in affecting cancer susceptibility and tumor progression, particularly in colorectal cancers. However, emerging evidence suggests that they are also integral components of the tumor tissue itself in a broad range of cancer types, such as pancreatic cancer, lung cancer, and breast cancer. Microbial features are linked to cancer risk, prognosis, and treatment responses, yet the biological functions of tumor-resident microbes in tumor progression remain unclear.

To address this knowledge gap, the team at Westlake Laboratory of Life Sciences and Biomedicine in Zhejiang used a mouse model of breast cancer with significant amounts of bacteria inside cells. They found that “passenger bacteria” travels through the circulatory system with cancer cells, modulating the cellular actin network and promoting cell survival against mechanical stress in circulation.

“Our study reveals that the cancer cell’s behavior is also controlled by the microbes hiding inside tumors, the majority of which were originally thought to be sterile,” says senior author Shang Cai of the Westlake Laboratory of Life Sciences and Biomedicine. “This microbial involvement is distinct from the genetic, epigenetic, and metabolic components that most cancer drugs target.”

Whether these microbes are passengers or drivers of tumor progression is an intriguing question. “Tumor cells hijacked by microbes could be more common than previously thought, which underscores the broad clinical value of understanding the exact role of the tumor-resident microbial community in cancer progression,” Cai adds.

The team was initially surprised that a low abundance of bacteria played such a crucial role in cancer metastasis. “What is even more astonishing is that only one shot of bacteria injection into the breast tumor can cause a tumor that originally rarely metastasizes to start to metastasize,” Cai says. “Intracellular microbiota could be a potential target for preventing metastasis in broad cancer types at an early stage, which is much better than to have to treat it later on.”

Cai says the findings, which were reported recently in the journal Cell, do not suggest antibiotics will provide treatment benefit, but how managing intratumor bacteria could improve cancer treatment in the future is an “important scientific question.”

Further in-depth analysis of how bacteria invade tumor cells, how intracellular bacteria are integrated into the host cell system, and how bacteria-containing tumor cells interact with the immune system could provide insights on how to properly implement antibiotics for cancer therapeutics in the clinic.