Effects of non-motorized voluntary running on experimental and spontaneous metastasis in mice

The present study investigated the effects of non-motorized voluntary running on experimental metastasis of B16BL/6 melanoma and spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice. After 9 weeks of running, mice (n=30 per group) received an intravenous injection of B16BL/6 cells or a subcutaneous injection of LLC cells, and then they were continued with their running activities. Experiments were terminated 2 weeks after the intravenous injection of B16BL/6 cells or 2 weeks after surgical removal of the primary tumor from mice subcutaneously injected with LLC cells. Mice in the running group ran an average of 4-6 km/day for the duration of the experiment. Voluntary running reduced body weight compared with the sedentary controls, but there were no differences in the number and size of lung metastases between groups with either model. Voluntary running significantly reduced plasma insulin and leptin levels and increased adiponectin level in mice with and without LLC compared with the sedentary controls. Having LLC significantly increased plasma concentrations of vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), PDGF-AB and monocyte chemotactic protein-1 (MCP-1) in mice. Voluntary running significantly increased plasma PDGF-BB and PDGFAB, but not VEGF and MCP-1, in mice with LLC compared to their sedentary counterparts. In conclusion, non-motorized voluntary running was favorable to body weight and the expression of related adipokines, but at 4-6 km/day it did not affect either experimental or spontaneous metastasis in mice.