Characterization of natural killer cells in colorectal tumor tissue of rats fed a control diet or a high-fat diet

Abstract

Background: Obesity is a major public health problem with an increasing prevalence reaching pandemic levels. The incidence and mortality for colorectal cancer is augmented in overweight and obese individuals. Previous studies demonstrated an impaired number, phenotype and functionality of natural killer (NK) cells under obese conditions. So far, the influence of obesity on NK cells in colorectal cancer tissue remained unclear. Therefore, the aim of the study was to investigate the occurrence and localization of NK cells in colorectal tumors of normal weight and diet-induced obese rats.

Methods: Wistar rats were fed a normal-fat diet (control) or a high-fat diet (HFD) to induce obesity. In half of the experimental groups azoxymethane (AOM) was injected to induce colorectal cancer. Tumors in colon and rectum were histopathologically classified in adenomas and adenocarcinomas and immunohistologically stained with the rat NK cell marker CD161. Occurrence and localization of NK cells were analyzed and quantified in the tunica mucosa and tunica submucosa of colorectal adenomas and the tunica submucosa of colorectal adenocarcinomas.

Results: NK cells are localized in the tunica mucosa and the tunica submucosa of colorectal tumors with NK cell accumulations as follicle-like aggregates especially in regions of the lamina muscularis mucosae and the lamina propria mucosae of the tunica mucosa as well as in regions of the tunica submucosa adjacent to the lamina muscularis mucosae. Although not statistically significant, the CD161 staining was clearly reduced in the tunica mucosa of colorectal tumors of rats fed a HFD compared to rats fed a control diet. Moreover, the CD161 staining in the tunica mucosa was positively correlated with the final body weight of AOM-treated rats independent of the supplied diet.

Discussion: For the first time, these results provide information about the localization and quantity of NK cells in colorectal tumor tissue of rats fed a control diet or high-fat diet. The slight reduction of NK cell number in colorectal tissue of rats fed a high-fat diet may contribute to an impaired tumor defense and the increased colorectal tumor outcome in diet-induced obese rats.

Keywords: Colorectal cancer; Immunohistochemistry; Natural killer cells; Obesity.