Abstract
Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.
Highlights
Colon cancer remains the second leading cause of cancer-related deaths in the UnitedStates with an estimated 104,270 new cases and 52,980 deaths in 2021 [1]
Despite the apparent increase in basal inflammation, we showed in a previous study that these Selenof-KO mice produce significantly fewer aberrant crypt foci (ACF) than littermate control mice when exposed to the colonspecific chemical carcinogen azoxymethane (AOM) [26]
Whereas effects of Selenof -expression in lung cancer cell lines resulted in minimal effects, the effects of Selenof in colorectal cancer appeared to be much more substantial [17,18,24]
Summary
Colon cancer remains the second leading cause of cancer-related deaths in the UnitedStates with an estimated 104,270 new cases and 52,980 deaths in 2021 [1]. The number of ACF is thought to have a strong relationship with the number of tumors formed in the colon [2], with about 20–30% of ACF predicted to develop into tumors. Intestinal inflammation is known to promote colorectal cancer through a variety of different mechanisms [3,4,5]. These include pro- and anti-inflammatory cytokines, oxidative stress, and even the composition of the intestinal microbiota [6]. Many of these mechanisms are thought to be modulated by dietary selenium [7,8,9]
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