Abstract 898: Exercise inhibits the growth of breast cancer and reduces fat mass in postmenopausal obese mice associated with a circulating angiostatic phenotype and the inhibition of angiogenesis in those tissues

Abstract

Abstract Obesity and physical inactivity are important risk factors for cancers, especially for postmenopausal breast cancer. However, potential mechanisms of exercise in reducing obesity and preventing postmenopausal breast cancer are poorly understood. The animal models in this area are very limited. In the present study, we used a postmenopausal obese mouse model inoculated with mouse breast cancer (E0771) cells to examine the potential effects of long-term exercise in reducing fat mass and breast cancer progression. Ovariectomy (OVX) was performed in 12 sixty week-old female mice (C57BL/6J), then followed by a high-fat (60%) diet for 12 weeks. In the eighth week of the dietary program, the body weight (BW) was significantly increased from 32.1±1.8 to 42.5±2.3 g; P<0.01), then 10^6 E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland. The mice were randomized into two groups, exercise and sedentary (n = 6). The exercise was conducted in a voluntary running cage system, i.e., 19.7±2.8 m/min, 30 min in the morning and 30 min in the afternoon, 7days/week, for 4 weeks. The lean mass (LM) or fat mass (FM) composition was monitored by EchoMRI weekly. In the end of experiment, the mice were anesthetized by isoflurane 2 hours after the last exercise, and blood samples, visceral fat and tumors were collected for measuring the expression of endostatin, sFlt-1 and free-VEGF using ELISA and blood vessel density (BVD) using CD31 immunochemistry. There was a significant decrease in BW (40.5±1.9 vs. 45.7±2.3 g; P<0.01) and tumor weight (1.95±0.41 vs. 2.63±0.11 g; P<0.01) in exercised-group compared to sedentary group, respectively. Exercise significantly decreased FM (17.8±0.9 vs. 22.7±1.1 g; P<0.01), tumor VEGF levels (44.1±2.1 vs. 65.4±3.3 pg/mg protein; P<0.01), and BVD (147.2±6.3 vs. 168.3±5.1 BV#/mm^2; P<0.01) in comparison with the sedentary, respectively. Exercise significantly decreased a ratio of capillaries to adipocytes of visceral fat in comparison with sedentary group (0.63±0.02 vs. 0.89±0.05; P<0.01). Exercise significantly increased endostatin (33.3±1.6 vs. 24.1±1.2 ng/ml; P<0.01) and sFlt-1 (59.5±3.1 vs. 48.3±2.5 pg/ml; P<0.05), and decreased free-VEGF (42.5±2.1 vs. 61.3±3.1 pg/ml; P<0.01) in the circulation in comparison with sedentary group, respectively. In postmenopausal obese mice, a long term exercise significantly 1) inhibited breast tumor angiogenesis and growth, 2) limited fat mass accumulation by reducing a ratio of capillaries to adipocytes, and 3) induced a circulating angiostatic phenotype characterized by increased endostatin and sFlt-1 and decreased free VEGF. These findings support the hypothesis that exercise-induced circulating angiostatic phenotype may contribute to the prevention of breast cancer progression and obesity in postmenopausal women. Citation Format: Shelby A. Cole, Jian-Wei Gu. Exercise inhibits the growth of breast cancer and reduces fat mass in postmenopausal obese mice associated with a circulating angiostatic phenotype and the inhibition of angiogenesis in those tissues. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 898. doi:10.1158/1538-7445.AM2015-898