Editors' ChoiceCOLORECTAL CANCER

A sticky (synergistic) situation

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Science Translational Medicine  27 May 2015:
Vol. 7, Issue 289, pp. 289ec84
DOI: 10.1126/scitranslmed.aac5084

Bad luck aside, environmental factors largely contribute to the risk of colorectal cancer, the third most common cancer worldwide. Complementing the list of usual suspects (e.g., diet, smoking, physical inactivity), investigators from Johns Hopkins Medical Institutions have identified bacterial biofilms within the colon as a risk factor for colorectal cancer. Biofilms are dense aggregates of microorganisms embedded within a sticky, self-produced matrix of extracellular polymeric substances, producing an environment that allows bacterial communities to thrive (think dental plaque). In a previous study, the investigators found that colonic biofilms correlate with enhanced host epithelial cell inflammation and proliferation. Here, in collaboration with The Scripps Research Institute, the investigators used a series of targeted and untargeted metabolomics experiments in paired colon cancer and histologically normal tissues from patients with colorectal cancer who underwent surgery to examine the influence of bacterial biofilms on the host colon tissue metabolome.

Acetylated polyamines, particularly N1, N12-diacetylspermine, were identified as being among the top up-regulated metabolites in colon cancer tissues. Polyamines are already known to boost cell growth and cancer formation. In this study, the authors found that biofilms—associated with both cancer tissues and paired normal tissues—enhanced up-regulation of acetylated polyamine metabolites compared with biofilm-negative tissues. Nanostructure imaging mass spectroscopy validated the localization of polyamine metabolites at the mucosal edge of cancer tissues in the vicinity of the biofilms. Furthermore, tissues of patients given antibiotics prior to surgery revealed no biofilms and much lower concentrations of N1, N12-diacetylspermine compared with biofilm-positive tissues. Taken together, this study suggests that colonic bacterial biofilms promote carcinogenesis through the up-regulation of acetylated polyamines. The investigators propose a model in which both host-derived and bacterial-derived polyamines synergistically promote biofilm formation and enhance conditions for cancer development, thus providing an avenue for future interventions that target both polyamine and biofilm production.

C. H. Johnson et al., Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab. 10.1016/j.cmet.2015.04.011 (2015). [Abstract]

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