Abstract 5913: The impact of daily exercise on tumor perfusion

Abstract

Abstract Aberrant blood vessel networks in solid tumors lead to impaired tissue perfusion and areas of hypoxia (pO2 < 10 mmHg). Tumor hypoxia is associated with aggressive progression, dissemination, and therapeutic resistance. It is found in 40% of breast cancers, and can constitute a major obstacle to anticancer therapy. Exercise is associated with improvements in cardiovascular and respiratory function, aerobic capacity and overall health. In cancer patients undergoing therapy, exercise has been shown to decrease treatment related side effects and general fatigue. The goal of the present investigation was to determine whether aerobic exercise could be applied to improve tumor perfusion and oxygenation in a breast cancer model. Such modulation of the tumor physiology and host environment would be expected to lead to enhanced antitumor efficacy when combined with radiotherapy or chemotherapy. The effects of a single and daily bouts of moderate intensity treadmill running were studied in mice bearing the syngeneic murine mammary carcinoma 4T1. The exercise intensity was determined by measuring the anaerobic threshold, which was assessed by measuring the steady rise in blood lactate during exercise. Initial studies examined the effect of a single moderate bout of exercise (18 m/min) in mice bearing ~500 mm3 orthotopic tumors. In subsequent experiments mice were exercised at 18 m/min, 5 days a week, for 8 weeks prior to orthotopic injection of tumor cells and continued exercise (5 days a week) for 2 weeks during tumor growth. Controls for each treatment consisted of sedentary mice exposed to a stationary treadmill for the equivalent amount of time. At the end of each of the exercise regimen, tumors were harvested, sectioned, stained, and tile mapped to assess physiological changes by immunofluorescence. The detection of open blood vessels (Hoechst-33342) was used as an indirect indicator of perfusion. Tumor hypoxia was determined using the 2-nitroimidazole (EF5). Blood vessels were stained using the endothelial cell marker CD-31. All markers were quantified using Photoshop and ImageJ NIH software. Our results indicate that in the 4T1 breast cancer model moderate intensity exercise did not significantly alter tumor growth, oxygenation or blood vessel number. However, daily bouts of exercise did significantly increase the number of open tumor vessels indicating improved tumor perfusion. These results suggest that a daily exercise regimen may have the potential to improve drug delivery to mammary tumors Citation Format: Jennifer M. Wiggins, Sharon Lepler, Christine Pampo, Lori Rice, Jennifer A. Lee, Dietmar Siemann. The impact of daily exercise on tumor perfusion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5913. doi:10.1158/1538-7445.AM2017-5913