A team led by scientists at The Scripps Research Institute (TSRI) and Johns Hopkins University School of Medicine has uncovered a big clue to how bacteria may promote some colon cancers.<\/p>\n
The study used novel metabolomic technologies to reveal molecular evidence suggesting a vicious circle in which cancerous changes in colon cells promote the growth of bacterial conglomerations called biofilms, and biofilms in turn promote cancer development.<\/p>\n
On the whole, the findings suggest that removing bacterial biofilms could be a key strategy for preventing and treating colon cancers, which currently kill about 50,000 Americans per year. The study also revealed an apparent metabolic marker of biofilm-associated colon cancers.<\/p>\n
The research, which used sophisticated \u201cmetabolomics\u201d techniques, 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.<\/p>\n
A previous study led by Sears and colleagues provided evidence that the tissue in and around cancers of the ascending colon, on the right side of the abdomen, almost always harbours bacterial conglomerations called biofilms.<\/p>\n
\u201cIn the current study, we wanted to understand more about what was happening,\u201d 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. \u201cIn particular, we wanted to determine if there was a metabolic link between the biofilm and colon cancer.\u201d<\/p>\n
Metabolites are small molecules in blood and tissues that are products of the myriad metabolic processes in cells. More than 10,000 distinct metabolites normally can be found in humans.<\/p>\n
The team began the search with an \u201cunbiased screen,\u201d a wide-net technique\u2014using advanced liquid chromatography and mass spectrometry and their XCMS metabolomic cloud-based platform\u2014that registered the levels of thousands of metabolites in a set of colon tissue samples from patients at Johns Hopkins and at the Karolinska Institute in Sweden.<\/p>\n
The data showed that polyamines were important in general and one metabolite\u2014N1, N12-diacetylspermine\u2014was particularly prominent, on average about nine times more abundant in cancerous tissue, compared to nearby non-cancerous tissue.<\/p>\n
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 its overproduction.<\/p>\n
With a sophisticated technique called \u201cnanostructure imaging mass spectrometry\u201d (NIMS), the team was able to map the precise locations of N1, N12-diacetylspermine in tissue samples, confirming its higher levels in both tumours and biofilms.<\/p>\n
The researchers also carried out a technique called \u201cglobal isotope metabolomics,\u201d using an isotope of N1, N12-diacetylspermine to trace its metabolic fate in cells in an unbiased manner, finding that it appears to be a metabolic end-product.<\/p>\n
That colon tumours would produce abnormally high amounts of N1, N12-diacetylspermine is not surprising. The molecule belongs to a family of metabolites called polyamines, which are known to have roles in driving cell growth and which are commonly up-regulated in cancers as well as in healthy fast-growing tissues. N1, N12-diacetylspermine itself has been observed at higher levels in colon cancer and is considered a potential biomarker for early cancer diagnosis.<\/p>\n
But why would bacterial biofilms also be linked to higher levels of N1, N12-diacetylspermine? It turns out that bacteria, too, use polyamines to drive their own cells\u2019 proliferation and to build biofilms. Polyamines are such ancient, ubiquitous molecules that bacteria apparently can even use those produced by their animal hosts.<\/p>\n
Thus, biofilms may promote cancer in the colon by inducing chronic inflammation and associated cell proliferation. That increased cell proliferation would be accompanied by a rise in the production of polyamines. Resident bacteria, in turn, could use this abundance of polyamines to make more biofilms\u2014completing the vicious circle. Along the way, levels of the by-product N1, N12-diacetylspermine would be driven higher and higher.\nThe Scripps Research Institute<\/link>\n","protected":false},"excerpt":{"rendered":"
A team led by scientists at The Scripps Research Institute (TSRI) and Johns Hopkins University School of Medicine has uncovered a big clue to how bacteria may promote some colon cancers. The study used novel metabolomic technologies to reveal molecular evidence suggesting a vicious circle in which cancerous changes in colon cells promote the growth […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1417"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=1417"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1417\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=1417"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=1417"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=1417"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}