title: Macrophage iron homeostasis and polarization in the context of cancer.
abstract: Macrophages are central in regulating iron homeostasis, which is tightly linked to their versatile role during innate immunity. They sequester iron by phagocytosis of senescent erythrocytes and represent a major source of available iron in the body. Macrophage iron homeostasis is coupled to the functional heterogeneity and plasticity of these cells, with their extreme roles during inflammation, immune modulation, and resolution of inflammation. It is now appreciated that the macrophage polarization process dictates expression profiles of genes involved in iron metabolism. Therefore, macrophages have evolved a multitude of mechanisms to sequester, transport, store, and release iron. A new, enigmatic protein entering the iron scene and affecting the macrophage phenotype is lipocalin-2. Iron sequestration in macrophages depletes the microenvironment, thereby limiting extracellular pathogen or tumor growth, while fostering inflammation. In contrast, iron release from macrophages contributes to bystander cell proliferation, which is important for tissue regeneration and repair. This dichotomy is also reflected by the dual role of lipocalin-2 in macrophages. Unfortunately, the iron release macrophage phenotype is also a characteristic of tumor-associated macrophages and stimulates tumor cell survival and growth. Iron sequestration versus its release is now appreciated to be associated with the macrophage polarization program and can be used to explain a number of biological functions attributed to distinct macrophage phenotypes. Here we discuss macrophage iron homeostasis with a special focus on lipocalin-2 related to the formation and function of tumor-associated macrophages.
authors.affiliation: Institute of Biochemistry I/ZAFES, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Jung
authors.affiliation: Institute of Biochemistry I/ZAFES, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Mertens
authors.affiliation: Institute of Biochemistry I/ZAFES, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. Electronic address: b.bruene@biochem.uni-frankfurt.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brüne
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D007501:Iron
keywords: Iron homeostasis; Lipocalin-2; Macrophage polarization; Tumor progression