Glutaminase 2 influence on tumor: macrophage interaction and metastasis

Abstract

Our main goal is to understand the role of GLS2 on breast cancer progression. For such, we want to answer the following questions:Do M1 and M2 macrophages influence in vitro metastasis of GLS2 expressing cells? GLS2 has been more often linked to anti-tumorigenic effects, mainly in hepatocarcinomas and gliomas. We found a link between GLS2 expression and diminished breast cancer patient survival; moreover, tissues with higher GLS2 expression presented altered pathways linked to cytoskeleton remodeling and epithelial-to-mesenchymal transition, traditionally linked to increased metastasis. Investigating the link between GLS2 and M1 and M2 macrophages on an in vitro invasion assay could help answer if GLS2 expression has a direct link with a worse prognosis in breast cancer.Second, is GLS2 expression directly linked to increased M2 (and decreased M1) macrophage infiltration on xenographic tumors? The importance of tumor microenvironment on tumor progression has been long known. Studying the influence of GLS2 expression on the recruitment and/or macrophage differentiation in vivo will be of great importance to understand whether this enzyme may have a direct effect on tumor progression in vivo. (AU)