Abstract
In addition to providing essential molecules for the overall function of cells, metabolism plays an important role in cell fate and can be affected by microenvironmental stimuli as well as cellular interactions. As a specific niche, tumor microenvironment (TME), consisting of different cell types including stromal/stem cells and immune cells, is characterized by distinct metabolic properties. This review will be focused on the metabolic plasticity of mesenchymal stromal/stem cells (MSC) and macrophages in TME, as well as on how the metabolic state of cancer stem cells (CSC), as key drivers of oncogenesis, affects their generation and persistence. Namely, heterogenic metabolic phenotypes of these cell populations, which include various levels of dependence on glycolysis or oxidative phosphorylation are closely linked to their complex roles in cancer progression. Besides well-known extrinsic factors, such as cytokines and growth factors, the differentiation and activation states of CSC, MSC, and macrophages are coordinated by metabolic reprogramming in TME. The significance of mutual metabolic interaction between tumor stroma and cancer cells in the immune evasion and persistence of CSC is currently under investigation.
Highlights
Cells constituting tumor microenvironment (TME), such as immune cells, endothelial cells, fibroblasts, and mesenchymal stromal/stem cells (MSC), communicate with cancer cells mutually influencing properties of each cell type and overall outcome of tumor growth [1]
In TME, cancer cells are able to reprogram their metabolism according to their needs and they can reprogram the metabolism of surrounding cells to respond to their demands and fuel tumor growth [4, 5]
Lactate, excreted by more differentiated cancer cells that are dependent on glycolysis, may in return serve as fuel for oxidative phosphorylation (OXPHOS) in cancer stem cells (CSC) that depend on mitochondrial metabolism, establishing a metabolic symbiosis system [12, 14] (Figure 1A)
Summary
Jelena Krstic1,2*, Drenka Trivanovic, Aleksandra Jaukovic, Juan F. Reviewed by: Kawaljit Kaur, University of California, Los Angeles, United States. Tumor microenvironment (TME), consisting of different cell types including stromal/stem cells and immune cells, is characterized by distinct metabolic properties. This review will be focused on the metabolic plasticity of mesenchymal stromal/stem cells (MSC) and macrophages in TME, as well as on how the metabolic state of cancer stem cells (CSC), as key drivers of oncogenesis, affects their generation and persistence. Besides well-known extrinsic factors, such as cytokines and growth factors, the differentiation and activation states of CSC, MSC, and macrophages are coordinated by metabolic reprogramming in TME. The significance of mutual metabolic interaction between tumor stroma and cancer cells in the immune evasion and persistence of CSC is currently under investigation
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