title: A red meat-derived glycan promotes inflammation and cancer progression.
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.
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Annie N
authors.initials: AN
authors.lastname: Samraj
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Oliver M T
authors.initials: OM
authors.lastname: Pearce
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Heinz
authors.initials: H
authors.lastname: Läubli
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Alyssa N
authors.initials: AN
authors.lastname: Crittenden
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Bergfeld
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Banda
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gregg
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Bingman
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Patrick
authors.initials: P
authors.lastname: Secrest
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Diaz
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093 Pathology, and.
authors.forename: Nissi M
authors.initials: NM
authors.lastname: Varki
authors.affiliation: Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093 Departments of Medicine, a1varki@ucsd.edu.
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D018450:Disease Progression; D005504:Food Analysis; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008114:Liver Neoplasms, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008460:Meat / Q000009:adverse effects* / Q000032:analysis*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006899:Mixed Function Oxygenases / Q000172:deficiency / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000032:analysis; D009438:Neuraminic Acids / Q000009:adverse effects* / Q000032:analysis / Q000276:immunology; D012307:Risk Factors
chemical_list: D019138:Antibodies, Blocking; D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid; D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase; D019158:N-Acetylneuraminic Acid
keywords: N-glycolylneuraminic acid; red meat and cancer; tumor-associated carbohydrate antigen; tumor-associated inflammation; xenosialitis