Abstract
Obesity is a widely spread disease and a crucial risk factor for malign disorders, including breast cancer of women in the postmenopause. Studies demonstrated that in case of obesity crucial natural killer (NK) cell functions like combating tumor cells are affected. This study aims to analyze NK cells and NK cell receptor expression of obese mice in a model for postmenopausal breast cancer. Therefore, female BALB/c mice were fed either a high fat or a standard diet. Thereafter, ovaries were ectomized and a syngeneic and orthotopical injection of 4T1-luc2 mouse mammary tumor cells into the mammary adipose tissue pad was performed. Obese mice showed increased body weights and visceral fat mass as well as increased levels of leptin and IL-6 in plasma. Moreover, compared to the lean littermates, tumor growth was increased and the NKp46-expression on circulating NK cells was decreased. Furthermore, the activating NK cell receptor NKG2D ligand (MULT1) expression was enhanced in adipose tissue of obese tumor bearing mice. The present study gives novel insights into gene expression of NK cell receptors in obesity and aims to promote possible links of the obesity-impaired NK cell physiology and the elevated breast cancer risk in obese women.
Highlights
Obesity represents a major health problem in numerous countries, as the prevalence for obesity is continuously rising worldwide
The susceptibility to infections is increased in obese individuals and overweight and obesity are discussed as crucial risk factors for a variety of cancer types, including esophageal, colorectal, gallbladder, pancreatic, liver, postmenopausal breast, ovarian, endometrial, kidney and prostate c ancer[7,8]
In the long-term experiment, tumor growth was monitored by bioluminescence imaging and NK cell receptor natural killer group 2 member D (NKG2D) as well as the ligands UL16-binding protein-like transcript 1 (MULT1) and retinoic acid early inducible-1 gene (Rae-1) were determined in adipose tissue of mice
Summary
Obesity represents a major health problem in numerous countries, as the prevalence for obesity is continuously rising worldwide. The functions of natural killer (NK) cells, which are an essential part of the innate immune system, represent 10 to 15% of the peripheral lymphocytes It is known, that they are impaired by leptin, which is secreted by the adipocytes and increases relative to the gain of body fat mass[23,24]. A recent study showed that lipid accumulation in NK cells from obese individuals is associated with the loss of NK cell cytotoxicity against tumor cells and could be restored by metabolic reprogramming[33] This indicates that there might be a promising link between impaired NK cell functions in obese individuals and the increased risk for cancer under obesity. The aim of the present study was to mimic postmenopausal breast cancer under diet-induced obese (DIO) conditions in a mouse model to investigate immune cell frequencies and associations between functional NKcell marker and tumor development in obesity. In the long-term experiment, tumor growth was monitored by bioluminescence imaging and NK cell receptor natural killer group 2 member D (NKG2D) as well as the ligands UL16-binding protein-like transcript 1 (MULT1) and retinoic acid early inducible-1 gene (Rae-1) were determined in adipose tissue of mice
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