Biochemical modulation of tumor-growth, metastasis and host metabolism

Exogenous nutrients, hormones and metabolites can significantly alter tumor growth, metastasis, and host nutritional status. Arginine, serine and methionine are critical amino acids required for protein, DNA and RNA synthesis and, thus, for cellular proliferation. To determine the effect of these specific amino acids on host metabolism, primary tumor growth and metastasis, 48 Lewis rats bearing the mammary adenocarcinoma MAC-33 were randomized to receive similar diets with 3% supplements of serine, arginine, methionine or glycine (control). After 25 days on each diet, animals were sacrificed to determine primary tumor biochemical composition and growth kinetics, number of lung metastases and carcass weight. A significant reduction in lung metastases occurred with serine and methionine supplementation (p<0.01) with no significant change in primary tumor size. However, increased mortality (p<0.001) and low carcass weight (p<0.05) were found in the methionine group indicating significant host toxicity. Serine-supplemented animals had a mortality rate and carcass weight comparable to the control group. Arginine supplementation had no effect on primary tumor growth, metastasis or carcass weight; however, increased mortality was observed in this group compared to controls. These results suggest that serine supplementation selectively supports host growth and inhibits metastasis in tumor-bearing animals. This study demonstrates the potential to differentially effect host and tumor growth with exogenous amino acid supplements.