Glutamine Targeting Inhibits systemic Metastasis in The VM-M3 Murine Tumor Model

Glutamine Targeting Inhibits systemic Metastasis in The VM-M3 Murine Tumor Model

Tumor metastasis being the leading cause of morbidity and mortality in cancer patients, targeted therapies have become increasingly popular, especially due to the multiple pathways involved in tumor cell survival. Cancer cells exhibit an increase in glycolysis and as a result, therapies are implemented to target the metabolism of glucose, including 2-deoxyglucose and calorie restriction. The efficacy of these glucose-based therapies has been demonstrated in multiple mouse and human brain cancer models, but it is apparent these cells also rely on glutamine for survival and growth.

This specific study aimed to analyze the effect of targeting glucose and glutamine, using a preclinical VM-M3 mouse model. The VM-M3 tumor cells exhibit the luciferase gene, to allow for the detection of growth and metastasis through bioluminescent imaging. A subcutaneous implantation site provides all the major marks of metastasis, such as detachment, intravasation into blood, immune attack, extravastation at thecapillary bed and growth. The researchers administered 25mM glucose, 4mM glutamine, and diazo-5-oxo-1-norleucine to the mice to analyze the purported effects. The VM-M3 cells demonstrated a greater reliance on glutamine, than glucose for energy and survival. When provided solely glucose, the cells were incapable of surviving in vitro. As for DON, it proved to be effective in limiting cell growth over 46 hours at low and high concentration.

Additionally, the effect of calorie restriction (CR) and DON on body weights and blood glucose levels was also assessed. The mice received 40% of normal intake, which significantly reduced the body weight and circulating glucose levels. However, mice treated with DON, body weight remained similar but declined the last three days of the study. Primary tumor growth was significantly lower in the CR and DON groups, though DON-treated groups had a significantly smaller tumor size compared to calorie restriction. When compared to both control and CR groups, DON-treated groups had no detectable metastasis to the liver, lung or kidney.

These results can be implemented for further investigation on targeting glutamine, which has shown to be the major energy substrate for cancer cells. Additional examination is required to understand the effects glutamine in other cancers that a epithelial oriented.

Zak BrennanComment