Abstract B24: Impact of aerobic exercise on tumor oxygenation and perfusion in breast cancer

Abstract

Abstract The purpose of this study is to evaluate the effects of low to moderate aerobic exercise on tumor vasculature, perfusion and oxygenation in breast cancer. Poor perfusion and hypoxia are common features of solid tumors that are a result of abnormal tumor angiogenesis. Both chemo- and radiation therapies are negatively affected by tumor hypoxia, with the presence of hypoxia associated with treatment failure and poor outcomes in cancer patients. While strategies to enhance tumor oxygenation and perfusion have been developed, their success in the clinic has been limited. A potential method to increase oxygenation and decrease hypoxia that is safe and well-tolerated is aerobic exercise. The benefits of exercise as a palliative measure are well documented, however the effects of exercise on tumor blood flow and oxygenation have not been extensively characterized. Histological analysis of vessel density (MECA-32), vessel perfusion (Hoechst-33342) and hypoxia (EF5) were quantified in tumor bearing mice subjected to low to moderate intensity treadmill running and compared to sedentary control mice. In a separate model, a murine dorsal skinfold window chamber model and in vivo microscopy of microvessel function was utilized to characterize changes in tumor vascular structure and function in real time. In these studies, the combination of hyperspectral imaging of hemoglobin (Hb) saturation and first-pass fluorescence (FPF) imaging of blood transit time were used. Hb saturation imaging reveals the oxygenation of blood within microvessels while FPF imaging gives information regarding blood flow and network connections by recording a fluorescent contrast agent as it is injected into circulation. Spectroscopic analysis was performed in female nude mice with surgically installed titanium window chambers. Mammary tumors were initiated in the windows and once tumors reached a specified volume, animals were subjected to daily treadmill running for up to a week. As a sedentary control, mice were placed on a stationary treadmill for equivalent periods of time. Combination imaging was performed daily to monitor microvessel oxygenation and blood flow. Preliminary results indicate that following one bout of exercise, tumor perfusion is increased, however there was no significant correlation between exercise and tumor microvessel oxygenation. For histological analysis, mammary tumors were initiated in the fat pad of female nude mice. Once tumors nodules were established, animals were subjected to either a single bout or daily bouts of exercise for 1 to 5 weeks. Sedentary controls were exposed to a stationary treadmill for equivalent periods of time. Following exercise protocols, tumors were harvested and sectioned for immunohistochemical analysis. Staining analysis revealed an improvement in tumor oxygenation and an increase in the number of perfused vessels in tumors of exercising animals in comparison to sedentary controls. Our results demonstrate aerobic exercise can increase tumor oxygenation and perfusion in breast cancer, suggesting that exercise can potentially be used as an adjunctive therapy to overcome tumor hypoxia and enhance the efficacy of chemo- and radiation therapy. Citation Format: Jennifer A. Lee, Jennifer Wiggins, Dietmar W. Siemann. Impact of aerobic exercise on tumor oxygenation and perfusion in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B24.