Abstract B46: The use of quantitative proteomics to increase the knowledge about metabolic symbiosis in a tumor microenvironment

Abstract

Abstract For more than a century, it is known that in a solid tumor, malignant cancer cells co-reside with stromal cells including fibroblasts and immune cells. In addition, changes in metabolic requirements of malignant cells are necessary to cover their high proliferative rate. Although it has been demonstrated that complementary metabolic functions of tumor cells and their supporting local stroma (e.g. cancer-associated fibroblasts, adipocytes) contribute to the progression of cancer, less is known about the metabolic needs of immune cells in this local tumor microenvironment. However, in the context of cancer, immune cells, including tumor-associated macrophages (TAMs) are of high interest since it is known that these cells are able to influence tumor progression by allowing the establishment of an attractive environment for tumor growth and metastasis. Studying the expression profiles of proteins involved in metabolic processes of these cells might be a good strategy to elucidate this question. In this study, we applied quantitative proteomics to study the differences in protein expression of TAMs vs. control macrophages (both bone marrow-derived and peritoneal macrophages) isolated from an in vivo murine model for non-small cell lung adenocarcinoma. In our peptide-centric two dimensional liquid chromatography (LC)- tandem mass spectrometry (MS/MS) setup where Tandem Mass Tag (TMT) labeling is applied, we were able to identify 1250 unique proteins, of which 1178 proteins were quantified with all six TMT reporter ions. Interestingly, analysis of the differentially expressed proteins indicate that several Gene Ontology terms regarding metabolic pathways including glutathione metabolic processes (p= 3.47 e-14) and pentose phosphate shunt (p= 2.29 e-8) were enriched. These data suggest that TAMs can reprogram their metabolism in order to survive to the oxidative stress existing in this kind of microenvironment. In conclusion, our results illustrate that proteome analysis is a good strategy to obtain insights in the biology of tumor-associated macrophages. Citation Format: Evelyne Maes, Mathias Wenes, Dirk Valkenborg, Inge Mertens, Hans Prenen, Massimiliano Mazzone, Geert Baggerman. The use of quantitative proteomics to increase the knowledge about metabolic symbiosis in a tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B46.