Abstract 3480: Potential impact of voluntary exercise on patterns of metastasis in a colorectal cancer model

Abstract

Abstract Background: Physical activity (PA) is associated with a lower risk of colorectal cancer (CRC) initiation and death from CRC. However, evidence for a causal link between PA and disease progression is lacking. This study assesses the effect of voluntary exercise on metastases formation in a novel pre-clinical mouse model for late-stage metastatic CRC. Methods: Murine colorectal tumor organoids were transplanted into the livers of immunocompetent C57Bl/6 mice using microsurgery. Animals were fed ad libitum. Voluntary exercise in tumor-bearing (TB) mice was modeled by offering running wheels for 0h/day (n=12), 3h/day (n=12) or 24h/day (n=12). Running wheel revolutions were cumulatively measured every 30min. PA was monitored by infrared cameras. Tumor progression was monitored using in vivo Bioluminescent Imaging. Food intake was measured by weighing. Body composition was monitored by echoMRI. All animals were sacrificed 12 weeks after tumor initiation. Results: We have developed a novel model for exploring the effects of exercise on metastatic tumor progression in CRC. The model combines micro-surgical transplantation of tumor organoids, yielding spontaneously metastasizing CRC, with voluntary exercise. Voluntary exercise in both exercise groups led to an on average running distances of 2,3±0,3 km/night (total 221±29 km) in TB-3h animals and 6,6±3,0km/night (total 600±290km) in TB-24h animals. TB-3h and TB-24h animals developed more lean mass and lower fat mass compared to sedentary animals. Intermittent exercise had no effect on primary tumor growth and reduced metastasis. Vigorous exercise increased primary tumor growth (229606±186012) compared to TB-3h (152821±125902) and sedentary animals (165171±250993). Moreover, vigorous exercise non-significantly increased lung metastasis formation (2382±3539) compared to intermittent exercise (753±852) and to sedentary (1333±2902), while reducing metastatic spread to the liver and the peritoneal cavity was found. Conclusions: These results suggest that exercise has the potential to influence the patterns and extent of metastasis in CRC, and that the degree of exercise is likely to be an important variable. Confirmation of these results in additional models, for instance using patient-derived organoids, is now warranted. Citation Format: Liza A. Wijler, Daniëlle A. Raats, Miriam van Dijk, Anne M. May, Onno Kranenburg. Potential impact of voluntary exercise on patterns of metastasis in a colorectal cancer model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3480.