A red meat-derived glycan promotes inflammation and cancer progression

Annie N. Samraj, Oliver M.T. Pearce, Heinz Läubli, Alyssa N. Crittenden, Anne K. Bergfeld, Kalyan Band, Christopher J. Gregg, Andrea E. Bingman, Patrick Secrest, Sandra L. Diaz, Nissi M. Varki, Ajit Varki, Stuart A. Kornfeld

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158 Scopus citations

Abstract

A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term consumption of "red meat" of mammalian origin. Although multiple theories have attempted to explain this human-specific association, none have been conclusively proven. We used an improved method to survey common foods for free and glycosidically bound forms of the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc), showing that it is highly and selectively enriched in red meat. The bound form of Neu5Gc is bioavailable, undergoing metabolic incorporation into human tissues, despite being a foreign antigen. Interactions of this antigen with circulating anti-Neu5Gc antibodies could potentially incite inflammation. Indeed, when human-like Neu5Gc-deficient mice were fed bioavailable Neu5Gc and challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Such mice are already prone to develop occasional tumors of the liver, an organ that can incorporate dietary Neu5Gc. Neu5Gc-deficient mice immunized against Neu5Gc and fed bioavailable Neu5Gc developed a much higher incidence of hepatocellular carcinomas, with evidence of Neu5Gc accumulation. Taken together, our data provide an unusual mechanistic explanation for the epidemiological association between red meat consumption and carcinoma risk. This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption.

Original languageEnglish
Pages (from-to)542-547
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number2
DOIs
StatePublished - Jan 13 2015

Keywords

  • N-glycolylneuraminic acid
  • Red meat and cancer
  • Tumor-associated carbohydrate antigen
  • Tumor-associated inflammation
  • Xenosialitis

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    Samraj, A. N., Pearce, O. M. T., Läubli, H., Crittenden, A. N., Bergfeld, A. K., Band, K., Gregg, C. J., Bingman, A. E., Secrest, P., Diaz, S. L., Varki, N. M., Varki, A., & Kornfeld, S. A. (2015). A red meat-derived glycan promotes inflammation and cancer progression. Proceedings of the National Academy of Sciences of the United States of America, 112(2), 542-547. https://doi.org/10.1073/pnas.1417508112