Technical Abstract: Dietary supplementation with methylseleninic acid reduces spontaneous metastasis of Lewis lung carcinoma in mice Lin Yan*, Lana C. DeMars The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA) on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice using intramuscular and subcutaneous injection models. Mice were fed AIN93G control diet or that diet supplemented with MSeA or selenomethionine (SeMet) at 2.5 mg selenium/kg for 4 weeks at which time they were injected intramuscularly or subcutaneously with 2.5 x 105 viable LLC cells. Experiments were terminated 2 weeks later for mice injected intramuscularly or 2 weeks after surgical removal of primary tumors from mice subcutaneously injected with cancer cells. Dietary supplementation with MSeA significantly reduced pulmonary metastatic yield compared with the controls (P < 0.05) in both models; however, SeMet treatment was without effect. Supplementation with MSeA significantly decreased plasma concentrations of urokinase-type plasminogen activator (P < 0.05) and plasminogen activator inhibitor-1 (P < 0.05). Furthermore, MSeA significantly reduced plasma concentrations of vascular endothelial growth factor (P < 0.05), fibroblast growth factor basic (P < 0.05) and platelet-derived growth factor-BB (P < 0.05) compared with the controls. Selenomethionine did not affect any of the aforementioned variables. These results demonstrate that MSeA reduces spontaneous metastasis of LLC in mice, perhaps through inhibition of the urokinase plasminogen activator system and reducing angiogenesis.