A new study found that a type of mouth microbes called fusobacteria can worsen colorectal tumors by sticking to a type of sugar found in tumorous growths. While previous studies have also found a link between bacteria and colorectal cancer, this particular study is the first to offer an explanation on just how exactly mouth bacteria attach to tumors. The study was conducted by researchers from the Harvard T.H. Chan School of Public Health and Hebrew University-Hadassah School of Dental Medicine and was published in Cell Host & Microbe on 10,August 2016.
Colorectal cancer (CRC) is one of the most common cancers in the United States responsible for at least a third of all cancer-related deaths. Although the exact causes of colorectal cancer remain unknown, studies did find some common risk factors that may be contributing to the development of CRC. Studies also found a link between microbes and CRC believing microbes could influence the development, progression, and outcomes of the disease. Furthermore, previous studies found that there are higher levels of fusobacteria in human colorectal tumorous growths in comparison with healthy tissue. Besides that, studies also found that fusobacteria increased the proliferation of cancer cells and even suppressed anti-tumor immunity and inhibited tumor killing by natural killer (NK) cells.
What makes this Study Different
Although the link between fusobacteria and CRC was well established through previous research, the exact mechanisms behind this were mostly unknown. The Harvard T.H. Chan School of Public Health and Hebrew University-Hadassah School of Dental Medicine study aimed to see if a type of sugar-binding protein called Fap2 was responsible for causing the growth of fusobacteria in the colon tumors and polyps of the intestinal tract. It is important to note that fusobacteria normally inhabit the mouth and are rarely found in the intestinal tract in most health people. One suggestion how fusobacteria get to CRC is that fusobacteria probably travel via the blood stream to these tumorous growths where they attached themselves to a type of sugar through a type of protein found on the surface of these bacteria.
Injecting Fusobacteria in Mouse Mdels
To see if this was the case, the research team examined two mouse models that either had precancerous growths or malignant tumors. They injected fusobacteria into their bloodstream to check if the bacteria would travel towards the tumors. According to their findings, the fusobacteria became saturated on the colorectal tumors in both mice models while the surrounding healthy tissue was not affected. The researchers also examined human metastatic cells of the liver. Colorectal cancer often spreads to the liver and these samples were used to see if the bacteria would attack to the colorectal metastasis to the liver which they apparently did.
The Role of Proteins and Sugars
Through further examination, the researchers found that the Fap2 protein which is found on the surface of fusobacteria binds to a type of sugar in the CRC called Gal-GalNac. This type of sugar is overexpressed in cancerous cells of the intestines as explained by the researchers. What this means is that Fap2 mediates the colonization of fusobacteria on colorectal tumors which might worsen the health outcomes of CRC patients. Considering that Fap2 was also found in previously held studies to impair the immune system’s capability to fight cancer, it was suggested that fusobacteria use this protein to bind to tumor cells and proliferate cancer cells.
What this Means for Cancer Patients
The strength of this study is that both animal and human models were used, but considering that mice have a different progression of colon cancer, the findings might not be that much comparable to the significantly different progression of colorectal cancer in humans. However, the discovery that sugar-binding proteins from bacteria that usually inhabit the mouth could exacerbate CRC is quite promising, especially in the development of future treatments. Wendy Garrett of the Harvard T.H. Chan School of Public Health and the Dana-Farber Cancer Center, and co-senior author of this study states that even though we probably cannot prevent mouth bacteria from entering the bloodstream, drugs that target either Fap2 or Gal-GalNac could prevent the bacteria from making cancer worse. However, more studies are needed before such treatments are proven to be effective.
Because colorectal cancer remains one of the deadliest cancers worldwide, research on this specific cancer is very much needed to increase patient survival rates. Screening for polyps and colorectal cancer has greatly improved patient outcomes, but more studies are needed to stop the cancer from getting worse in those who are already affected. Researchers from the Harvard T.H. Chan School of Public Health and Hebrew University-Hadassah School of Dental Medicine may be closest to the discovery of viable cancer treatments that target either the Fap2 protein found on fusobacteria or the sugar Gal-GalNac which is found in surprisingly large amounts in CRC tumors.