A red meat-derived glycan promotes inflammation and cancer progression.
نویسندگان
چکیده
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.
منابع مشابه
Corrigendum: Involvement of a Non-Human Sialic Acid in Human Cancer
Sialic acids are common monosaccharides that are widely expressed as outer terminal units on all vertebrate cell surfaces, and play fundamental roles in cell-cell and cell-microenvironment interactions. The predominant sialic acids on most mammalian cells are N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac). Neu5Gc is notable for its deficiency in humans due to a species-...
متن کاملMeat, Fish, Poultry, and Egg Intake at Diagnosis and Risk of Prostate Cancer Progression.
Little information exists on diet and prostate cancer progression. We examined the association between intakes of total red meat, processed and unprocessed red meat, poultry, fish, and eggs and prostate cancer recurrence. We conducted a prospective study of 971 men treated with radical prostatectomy for prostate cancer between 2003 and 2010. Men completed a food frequency questionnaire at diagn...
متن کاملGI highlights from the literature.
▸ Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Med 2013;19:576–85. Numerous studies have highlighted the contribution of the gut microbiota to diseases including cancer, inflammatory conditions such as metabolic disorders and also cardiovascular disease (CVD). Mechanistic studies have shown that th...
متن کاملThe Role of Cyclooxygenase-2 in Signaling Pathways Promoting Colorectal Cancer
Colorectal cancer is one of the most common cancers in the world. Various factors are involved in the development and progression of this disease. One of these agents is cyclooxygenase-2 (COX-2). COX-2 is a product of the PTGS2 gene and converts free arachidonic acid to prostaglandins. COX-2 is not naturally expressed in most normal cells. Noticeably, the increased expression of COX-2 has been ...
متن کاملThe Role of Inflammation and Changes of Adipose Tissue-Resident Immune Cells in Increasing the Risk of Cancer: A Narrative Review
The incidence of obesity, as a major health problem, has increased significantly over the past decades. This condition is associated with an increased risk of cancers, type 2 diabetes, and cardiovascular diseases. The current study aimed to investigate the effects of inflammation and changes of adipose tissue-resident immune cells on increasing the risk of cancer in obese individuals. In obesit...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 112 2 شماره
صفحات -
تاریخ انتشار 2015