A bacterial toxin may accelerate the spread of colorectal cancer to other parts of the body, according to a recent study published by He et al in Cell Host & Microbiome. The findings could pave the way for novel tools to detect metastatic colorectal cancer early and determine which patients may require more aggressive treatments.
Background
Colorectal cancer is the second-leading cause of cancer-related mortality in the United States; however, when it’s caught early, the 5-year relative survival rate is about 90%. Metastases are the primary cause of mortality from cancer, and treatment options in these patients remain limited.
The intestinal microbiota are microorganisms known to play a wide-ranging role in health, from digestion to regulation of the immune system. They may also influence the development and spread of several types of cancers, including colorectal cancer.
Campylobacter jejuni is one of the most common causes of foodborne illnesses, causing more than 2 million cases of diarrhea-related diseases per year in the United States. Some C jejuni species contain a toxin known as cytolethal distending toxin (CDT). Prior research has shown that this toxin may be essential to causing colorectal cancer in mice.
Study Methods and Results
In the recent study, researchers sought to uncover how C jejuni may affect the spread of cancer. They compared the presence of C jejuni in tissues from 34 patients with primary colorectal cancer who developed metastasis with 37 patients who did not develop metastasis within a 3-year follow-up period.
The researchers discovered a high number of the bacteria in the patients with metastasis. Of note, those with detectable levels of the bacteria had a poorer prognosis than did those without detectable levels of the bacteria. The researchers confirmed the findings in large national data sets of tumor samples.
“These findings confirmed that CDT is essential for the bacteria’s role in promoting cancer spread,” explained co–study author Christian Jobin, PhD, the Gatorade Distinguished Professor of Medicine at the University of Florida College of Medicine and Co-Leader of the Immuno-Oncology and Microbiome research program at the University of Florida Health Cancer Center. “When bacteria that produce CDT move to tumors outside the gut, it appears to accelerate the spread of these tumors,” he continued.
Using laboratory mice with metastatic lung and liver tumors, human colorectal cancer tissue, and three-dimensional colorectal cancer tumor models developed from patient cells, the researchers then showed how the bacterial toxin promoted the spread of cancer. They found that CDT led to an increased expression of several types of enzymes and activated a type of signaling in cancer cells associated with metastasis.
Conclusions
Several clinical trials are currently exploring drugs that interfere with this cell-signaling pathway. The researchers hope their findings can guide the development of novel therapies. “This work contributes to a new understanding of how bacterial toxins promote colorectal metastasis, opening novel screening approaches to predict at-risk patients,” emphasized Dr. Jobin.
The researchers also revealed that they recovered live bacteria from tumors outside the gut, suggesting the tumors created an environment that was friendly to their growth. More research may be needed to understand how the bacteria migrated to tumor sites and how the toxin activated the signaling pathways.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.
