(Disponível em Português)
Scientists have discovered that a microbe often abundant in colorectal cancer tumors is able to literally ride on tumors cancer cells and travel to distant parts of the body, possibly promoting metastatic growth at those sites.
A few years back, a bacterium called Fusobacterium nucleatum, that is usually found in the mouth (associated with dental plaque), was discovered to be abundantly present in colorectal cancers. This bacterium is now strongly suspected of influencing the development and growth of these cancers.
A new study now goes even further, showing that when F. nucleatum is found in a primary tumor in the gut, it is also found in metastases derived from that tumor. The results, which suggest that F. nucleatum may enhance the process of metastasization – and raise the question of one day adding antibiotics to the treatment regimen of these cancers –, have been published in the journal Science.
In a series of experiments, Matthew Meyerson, from Harvard Medical School and the Dana-Farber Cancer Institute, with colleagues from the US and Spain, tested the presence of the bacterium in samples of primary tumors and liver metastases which had been collected from the same patient. They found that only when F. nucleatum was present in the primary tumor was it also present – and alive – in the paired metastatic tissue. And they also showed, they write that the bacterial strains of F. nucleatum in primary and metastatic tissues from the same patient were “nearly identical”, despite the fact that the collection of each type of tissue had been carried out months, even years apart.
Lastly, in the metastatic liver tissue, F. nucleatum could be found in individual cancer cells. Overall, these results indicate that the microbe harbored by the initial colorectal tumor had migrated to the liver along with malignant cells.
Next, the team wanted to determine, in an animal model of the disease, the impact that an antibiotic course of treatment could have on colorectal cancer growth. This prompted them to transplant tissue from human colorectal cancers into immunodeficient mice to see if these so-called “patient-derived xenografts” would take root. In fact, only F. nucleatum-containing cancer tissue gave rise to successful xenografts, and the bacteria they contained remained viable through several successive generations of xenografts.
So what would happen to these patient-derived tumors, they now asked, if they gave the animals an antibiotic to which F. nucleatum is highly sensitive, called metronidazole? Would this affect tumor growth?
Oral administration of metronidazole to mice whose xenografts contained F. nucleatum, the authors write, resulted in a statistically significant decrease in tumor growth and was associated with a significant decrease in F. nucleatum load in the tumor tissue, as well a a significant reduction in tumor cell proliferation.
The results “point to the potential of Fusobacterium (…) to contribute to colorectal cancer growth and metastasis”, the authors conclude. “We hypothesize that Fusobacterium travels with the primary tumor cells to distant sites, as part of metastatic tissue colonization”. The microbes are thus “intrinsic and essential” components of the cancer.
However, before giving antibiotics to patients with colorectal cancers containing F. nucleatum, the scientists caution that further studies are warranted. In particular, because the broad impact of these drugs on normal, healthy gut bacteria could in fact prove negative. “Ideally, one would want to develop a Fusobacterium-specific antimicrobial agent to assess the effect of selective targeting of Fusobacterium on tumor growth.”
According to recent data from the World Health Organization, colorectal cancer is the second most common cause of cancer in women and the third most common in men. It is also the fourth most common cause of cancer death after lung, stomach, and liver cancer.
Ana Gerschenfeld works as a Science Writer at the Science Communication Office at the Champalimaud Neuroscience Programme
Edited by: Catarina Ramos(Science Communication office). Photo credit: mostly*harmless(Creative Commons CC BY-NC 2.0)
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