The opposing impacts of dietary methionine restriction on tumor growth in immunodeficient and immunocompetent mice

Methionine, a sulfur-containing essential amino acid, is a key component of dietary proteins important for protein synthesis, sulfur metabolism, antioxidant defense, and signaling. However, the role of methionine in cancer progression remains inconclusive. On one hand, dietary methionine restriction is known to repress cancer growth and improve cancer therapy in xenografted tumors. On the other hand, methionine is also critical for T cell activation and differentiation, making it a potential tumor suppression nutrient by enhancing T cell-mediated anti-tumor immunity. Here we investigated the interaction between dietary methionine, immune cells, and cancer cells by allografting CT26.WT mouse colon carcinoma cells into immunocompetent Balb/c mice or immunodeficient NSG mice, then analyzed how dietary methionine contents affect their growth. Our results show that dietary methionine restriction suppresses tumor growth in immunodeficient NSG mice but promotes tumor progression in immunocompetentt Balb/c mice. Total RNA was extracted from allografted CT26.WT tumors isolated from mice fed with either a high methionine diet containing 0.86% methionine (0.86%) or a methionine restricted diet containing 0.172% methionine (0.172%). All RNA-seq libraries were prepared with the TruSeq Stranded/Ribo kit (Illumina, San Diego, CA) and sequenced using the single-end 76bp protocol at about 500 million reads per library using the NextSeq 500 platform (Illumina) per the manufacturer’s protocol.