A New Approach to Treating Colon Cancer

June 2015

A research team led by scientists at The Scripps Research Institute (TSRI) and Johns Hopkins University School of Medicine has discovered that bacterial conglomerations, called biofilms, may promote some colon cancers. The findings also suggest removing those biofilms could prove a key strategy for preventing and treating colon cancers – which currently kill about 50,000 Americans per year.

Authors of the new study included Caroline Johnson and Gary Siuzdak of TSRI's Center for Metabolomics.

Using novel metabolomic technologies, the study revealed molecular evidence suggesting cancerous changes in colon cells promote the growth of biofilms, which in turn promote cancer development by inducing chronic inflammation and associated cell proliferation. The study also revealed an apparent metabolic marker of biofilm-associated colon cancers.

The research was a collaboration between groups led by Gary Siuzdak, professor of chemistry, molecular and computational biology and senior director of the Scripps Center for Metabolomics at TSRI, Cynthia L. Sears, professor of medicine, oncology and molecular microbiology and immunology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, and David Edler, associate professor at the Karolinska Institute.

A previous study led by Dr. Sears and colleagues provided evidence that the tissue in and around cancers of the ascending colon almost always harbors these biofilms.

"In the current study, we wanted to understand more about what was happening," said Caroline H. Johnson, member of the Scripps Center for Metabolomics and co-first author of the new report with Christine M. Dejea of Johns Hopkins. "In particular, we wanted to determine if there was a metabolic link between the biofilm and colon cancer."

The team began registering the levels of thousands of metabolites – small molecules in blood and tissues that are products of the myriad metabolic processes in cells – in a set of colon tissue samples. More than 10,000 distinct metabolites can normally be found in humans. The data showed that one metabolite, N1, N12-diacetylspermine, was, on average, about nine times more abundant compared to nearby non-cancerous tissue.

In further tests, the team found that even among cancerous samples the same metabolite was four times more abundant in the presence of biofilms. In other words, the cancerous cells and the biofilms both seemed to be contributing to N1, N12-diacetylspermine's overproduction. Using "nanostructure imaging mass spectrometry" (NIMS), the team was able to confirm higher levels in both tumors and biofilms by mapping the precise locations of this metabolite.

The researchers carried out a technique called "global isotope metabolomics." Using an isotope to trace its metabolic fate in cells in an unbiased manner, they found that N1, N12-diacetylspermine appears to be a metabolic end-product.

As they continue in their research, the team hopes to discover more about the molecular pathways through which polyamines contribute to tumor growth and biofilm construction. Additionally, they'll seek to find why bacterial biofilms are found frequently in association with tumors of the ascending colon, but less frequently in tumors further along in the colon.

"We'd also like to look at samples from other populations that have a low level of colon cancer and different traditional diets, because we know that diet can influence polyamine levels," said Dr. Johnson.

In the meantime, treatment with antibiotics may be an option for removing colonic biofilms and reducing the cancer risks they bring. The scientists found that colon cancer samples from patients who had taken oral antibiotics 24 hours prior to surgery harbored no biofilms and no cultivable bacteria. Additionally, the samples exhibited significantly less N1, N12-diacetylspermine, on average, than samples from patients who had not taken antibiotics.

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