Tissue Distribution of Radiolabeled Tumor Cells in Wheel Exercised and Sedentary Mice

Abstract

During the process of metastasis tumor cells must interact with vascular endothelial cells, basement membrane, and extracellular matrix. Specifically, tumor cells must bind to adhesion molecules to extravasate from the circulation into the tissue. Expression of adhesion molecules is altered by cytokines, such as tumor necrosis factor and interleukin-1. Exercise has been reported to alter circulatory levels of these cytokines. We have recently shown that exercise training reduces the number of experimental metastases in mice following intravenous (i.v.) injection of tumor cells. Thus, it was of interest to determine if one possible mechanism of reduced metastasis in exercised mice was a reduction in the initial retention of tumor cells in the pulmonary circulation. C3H/He and (C3H/H3×BALB/c)F₁mice were given access to running wheels or remained sedentary for nine weeks after which ⁵¹Cr labelled CIRAS 1 tumor cells (5 × 10⁵ cells) were injected into a tail vein. Recovery of radioactivity in lungs, liver, spleen and kidney was assessed 5 min, 30 min, 90 min, 3 h and 24 h after injection. Wheel running mice displayed a lower retention of radioactivity in the lungs relative to sedentary mice 5min (F_1,34=11.91, p<0.002; W = 59.1±3.6%, S = 75.0±2.9%; Mean ± S.E.) and 30min (F_1,18= 64.00, p<0.001; W = 32.4±3.4%, S = 68.5±3.0%) post-injection. Radioactivity recovered in the lungs from wheel and sedentary mice was not significantly different at the other time points. Wheel exercised mice also had a small reduction in recovery of radioactivity from the liver, spleen and kidney at 30 min and 90min after injection (p<0.05). These data indicate that the initial arrest of tumor cells in the pulmonary vasculature of mice is reduced by regular wheel activity. The mechanisms for the differences in tumor cell arrest resulting from wheel exercise remain to be determined, but may involve alterations in the expression of cell adhesion molecules.

Key words

Exercise - hematogenous dissemination - tumor cell distribution - adhesion