Glutamine metabolism and its effect on the tumor microenvironment

• Grant number: 20/15727-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2021
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Paula Lepique
• Grantee: Larissa Fonseca Marques
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Although the literature indicates that tumor cells preferentially use the glycolytic pathway, there are tumors that use other substrates for metabolism, such as fatty acids and amino acids, including glutamine. The use of glutamine, by glutaminolysis, provides metabolic intermediates for the Krebs cycle, for the synthesis of macromolecules and for the redox balance. Tumor cells and immune cells share metabolic similarities and tumors are capable of modulating the immune response through competition for nutrients and the generation of metabolites that favors cell proliferation and tolerogenic mechanisms. Studies show that the inhibition of glutamine processing in macrophages present in the tumoral microenvironment negatively impacts the M2 phenotype, which potentially has pro-tumoral activity. In addition, it is known that M2 macrophages show greater expression of the enzyme Glutamine Synthase and that levels of Glutaminase mRNA are often found elevated in most human malignant cells. With that being said, this study seeks to prove the hypothesis that the inhibition of the glutamine metabolism enzymes leads to the reduction of tumor growth influenced by the change in the macrophages profile, the model lines used will be derived from cervical cancer, HeLa, which uses glutaminolysis, and C33A, exclusively glycolysis dependent.