Abstract
Many observational epidemiologic studies suggest an association between exercise and colon cancer risk. The mechanisms contributing to a preventative effect of exercise on colon cancer are complex and multifaceted. Altered immune system function is one possible mechanism that has been largely unexplored. Therefore, the purpose of this study was to examine the effects of exercise on markers associated with macrophages and select T cell populations in a mouse model of intestinal tumorigenesis and to relate this to polyp characteristics. Male ApcMin/+ mice were randomly assigned to either sedentary (Sed) or exercise (Ex) treatment (n=6–9/group). The exercise treatment consisted of treadmill running for 1 h/day and 6 days a week at 15 m/min from 4 until 16 weeks of age. Intestinal polyps were counted and categorized by size. Mucosal tissue was analyzed for mRNA expression of overall macrophages (F4/80), for genes associated with M1 (IL-12, IL-23 and Nos2) and M2 (CD206, IL-10, IL-4, CCL17, CCL22 and Arg-1) macrophages and the macrophage chemoattractants MCP-1, fetuin A and CXCL14. Markers for cytotoxic T cells (CTLs) and regulatory T cells were also examined by measuring mRNA expression of CD8 and Foxp3, respectively. While there was no significant difference in overall polyp number between the groups (Sed, 23.3±4.3; and Ex, 16.5±4.3), Ex did have a reduction in the number of large polyps (Sed, 6.1±1.1; and Ex, 3.0±0.6) (P<0.05). This was consistent with a decrease in spleen weight (P<0.05). Similarly, Ex reduced mRNA expression of overall macrophages (F4/80) as well as markers associated with both M1 (IL-12) and M2 (CD206, CCL22 and Arg-1) subtypes (P<0.05) but there was no significant decrease in macrophage chemoattractants. CD8 expression was increased while Foxp3 expression was decreased with Ex (P<0.05). Overall the data provide important new information on immune regulation as a possible mechanism for the documented benefits of exercise training on reducing colon cancer progression.
Highlights
Colon cancer remains a significant global health concern; it is the third most common malignancy and the fourth most common cause of cancer mortality [1,2,3,4]
It has been reported that ApcMin/+ mice develop cachexia that is positively correlated with polyp burden [32]
Given the role of T cell subsets in tumorigenesis, we performed gene expression analysis of markers associated with cytotoxic T lymphocytes (CTLs) (CD8) and Tregs (Foxp3) (Fi. 5)
Summary
Colon cancer remains a significant global health concern; it is the third most common malignancy and the fourth most common cause of cancer mortality [1,2,3,4]. It accounts for approximately 600,000 deaths worldwide. Physical inactivity has been reported to account for 10% of all colon cancer cases [6], whereas physical activity has been associated with reduced risk for incidence of colon cancer This inverse relationship between physical activity and colon cancer risk is supported by epidemiological studies as well as controlled experimental studies using rodent models. A recent study in a multiethnic colon cancer screening population reported that exercising for 1 h per week was associated with a lower prevalence of polyps and adenomas when compared to those who exercised less or not at all [8]
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