The gut contains trillions of microorganisms, but new research finds one bacterium that drives the growth of colorectal cancer cells.
The human gut normally hosts tens of trillions of diverse microorganisms. While these microbes are essential for human health, research has also shown a connection between some of the gut's bacteria and different intestinal diseases, including colorectal cancer.
Colorectal cancer is the second leading cause of cancer-related death in the United States, with approximately 140,000 U.S. individuals being diagnosed with the disease every year, and more than 50,000 people dying from it.
New research examines the link between a bacterium called Streptococcus gallolyticus subspecies gallolyticus (Sg) and colorectal cancer.
Previous studies have pointed to a link between colorectal cancer and Sg, but until now, it was not exactly clear if or how Sg promoted the condition.
Specifically, it was not known whether the bacterium itself actively drives colorectal cancer, or if Sg is rather a consequence of the disease - that is, if cancerous tumors are a favorable environment for the development of Sg.
The new study set out to examine the precise mechanism that may underlie the connection between Sg and colorectal cancer.
The first author of the study is Ritesh Kumar, of the Health Science Center of Texas A&M University in Bryan, and the findings were published in the journal PLOS Pathogens.
Sg actively promotes cancer proliferation
Kumar and colleagues examined in vitro human cell cultures and tissue from human tumors, as well as performing experiments in mice.
In cell cultures, the scientists grew colorectal cancer cells together with Sg. These experiments revealed that Sg helps colorectal cancer cells to proliferate. Additionally, they showed that Sg drives colorectal cancer cell proliferation depending on the growth phase of the Sg bacteria, and only when the bacteria and cancer cells are in direct contact.
The scientists also examined whether bacteria secretions or other metabolites from Sg would drive cancer cell proliferation, but they found that, on their own, these were not sufficient to promote cancer cell growth.
Additionally, the researchers investigated the effects of Sg on a protein known to play a crucial role in the development of colorectal cancer: the beta-catenin protein. As the authors explain, the "Wnt/beta-catenin signaling pathway regulates cell fate and proliferation and is a critical pathway in colon tumorigenesis."
The researchers therefore examined the effect of beta-catenin on responsive and unresponsive cells.
The tests showed that, when beta-catenin was inhibited, Sg did not drive the proliferation of cancer cells. This suggested to the researchers that Sg uses the beta-catenin signaling pathway to drive colorectal cancer cell proliferation.
Additionally, Kumar and team injected Sg into mice that had been engineered to develop colorectal cancer and monitored their tumor growth in comparison with a control group that was injected with a different bacterium.
The colorectal cancer mice that received Sg developed more tumors than the control mice. These mice also produced more beta-catenin, which indicates increased cancer severity.
Finally, the scientists also examined healthy tissue and tumor tissue from more than 100 people with colorectal cancer. They found that approximately 74 percent of tumor tissues were infected with Sg.
Until now, it had been suspected that people with colorectal cancer might have a latent Sg infection, but how prevalent Sg may have been among these patients was not sufficiently investigated. The authors conclude:
"[The findings] demonstrate that Sg actively promotes colon cancer cell proliferation and tumor growth, suggesting that it is not an innocent "passenger". These results represent a major step forward in understanding the relationship between Sg and CRC [colorectal cancer]."
Finally, Kumar and colleagues hope that with future research, they will gain a better understanding of the mechanisms that drive tumor formation, which will help scientists to improve "cancer diagnosis, prevention, and treatment."