A red meat-derived glycan promotes inflammation and cancer progression
Samraj AN, Pearce OM, Läubli H, Crittenden AN, Bergfeld AK, Banda K, Gregg CJ, Bingman AE, Secrest P, Diaz SL, Varki NM, Varki A
Proceedings of the National Academy of Sciences of the United States of America · 297 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- National Science Foundation
- Nonprofit
- Ellison Medical Foundation
- Nonprofit
- Cancer Research Institute
- University or hospital
- Harvard University
- University or hospital
- University of Cambridge
- Government
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Government
- National Institutes of Health
- Government
- National Cancer Institute
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- NIH HHS
- Government
- NIDDK NIH HHS
- Government
- NCI NIH HHS
- Government
- HHS | NIH | National Cancer Institute
- Grants
- National Cancer Institute (R01 CA 38701); National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK 069263); National Cancer Institute (R01 CA038701); National Institutes of Health (P51‐OD011132); National Institutes of Health (R01 CA38701)
Based on 13 listed funder(s).
Publication
- Published
- 2014-12-29 · Proc Natl Acad Sci U S A · vol. 112 · issue 2 · pp. 542–547
- Publisher
- National Academy of Sciences
- Cited
- 408 citations · more than 100% of similar papers · 45.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 68 works
- Access
- Free to read
- Research areas
- Milk Quality and Mastitis in Dairy Cows · melanin and skin pigmentation · Glycosylation and Glycoproteins Research
- Keywords
- Inflammation, Red meat, Sialic acid, Cancer, Biology, Immunology, Medicine, Internal medicine, Food science, Biochemistry
- MeSH
- animals, mice, congenic, mice, inbred c57bl, mice, knockout, humans, mice, liver neoplasms, experimental, disease progression, inflammation, neuraminic acids, n-acetylneuraminic acid, mixed function oxygenases, antibodies, blocking, risk factors, food analysis, meat, male
12 authors
From US
- Annie N. SamrajUniversity of California San Diego
- Oliver M.T. PearceUniversity of California San Diego
- Heinz Philipp LaubliUniversity of California San Diego
- Alyssa N. CrittendenUniversity of California San Diego
- Anne K. BergfeldUniversity of California San Diego
- Kalyan BandaUniversity of California San Diego
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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