The differential effect of glutamine supplementation on the orthotopic and subcutaneous growth of two syngeneic murine models of glioma

Abstract Objectives Glutamine serves as a major fuel source for tumor cell proliferation while simultaneously playing an essential role in maintaining gastrointestinal health and immune function. Controversy exists regarding glutamine supplementation for cancer patients undergoing chemotherapy and radiation, with concerns that it may stimulate cancer growth. The main purpose of the study was to examine the effects of dietary glutamine supplementation (0.4 g/kg/day) on the growth of malignant gliomas, which utilize large amounts of glutamine to satisfy metabolic demands. Methods Glutamine supplementation was administered in food (25 mg glutamine/25 g of chow/cage/day) and water (1.0 mg/mL) until endpoint. Brain bioluminescence and subcutaneous tumor volumes were used to assess the effect of glutamine supplementation on the growth of the syngeneic VM-M3 and CT-2A preclinical models of glioma. Results Glutamine supplementation had no significant effect on the orthotopic growth of the VM-M3 or the CT-2A gliomas when compared to non-supplemented controls. However, glutamine supplementation significantly increased tumor volume by 28 % in the VM-M3 and by 166 % in CT-2A tumors when grown subcutaneously outside the central nervous system (CNS). Additionally, glutamine supplementation increased serum glutamine despite a localized decrease in intra-tumoral glutamine concentrations. Conclusions The results show that glutamine administration at 0.4 g/kg per day in mice did not affect orthotopic tumor growth in the brain but increased tumor growth subcutaneously. Hence, caution is warranted when considering chronic, high-dose glutamine supplementation in patients with glutamine-dependent malignancies. Further studies are needed to better understand the potential risks and benefits of glutamine supplementation in cancer therapy.