Lipocalin-2 and iron trafficking in the tumor microenvironment. (June 2017)

• Record Type: Journal Article
• Authors: Jung, Michaela; Mertens, Christina; Bauer, Rebekka; Rehwald, Claudia; Brüne, Bernhard
• Is Part Of: Pharmacological research. Volume 120(2017:Jun.)
• Page Start: 146
• Page End: 156
• Publication Date: 2017-06
• Subjects: Bcl-2 B cell lymphoma 2 -- BDH1 3-hydroxybutyrate dehydrogenase, type 1 -- BDH2 3-hydroxybutyrate dehydrogenase, type 2 -- CD cluster of differentiation -- DHBA dihydroxybenzoic acid -- 2, 3-diDHBA 2, 3-dihydro-2, 3-dihydroxybenzoate -- DMT-1 divalent metal transporter-1 -- EMT epithelial-to-mesenchymal transition -- FTH ferritin heavy -- FTL ferritin light -- FPN ferroportin -- HAMP hepcidin -- hpx hypotransferrinemic -- IL interleukin -- IRP iron-regulatory proteins -- LIP labile iron pool -- Lcn-2 lipocalin-2 -- MMP-9 matrix metalloproteinase 9 -- MMTV mouse mammary tumor virus -- PyMT polyoma middle T antigen -- TAM tumor-associated macrophages -- Tcyt cytotoxic T cell -- Tf transferrin -- TfR transferrin receptor -- TH T helper cells -- Treg regulatory T cells; Iron -- Lipocalin-2 -- Macrophages -- Siderophores -- Tumor microenvironment -- Iron chelators; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2017.03.018
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Iron is an essential element for virtually all organisms. It facilitates cell proliferation and growth but also contributes to major hallmarks of cancer such as tumor initiation, growth, and metastasis. Often, iron handling of tumor cells is disturbed, with altered iron acquisition, efflux, and storage. Targeting perturbed iron metabolic pathways might open opportunities towards novel approaches in cancer treatment. It is becoming clear that cells of the tumor microenvironment such as macrophages contribute to tumor progression. Since macrophages evolved a multitude of mechanisms to sequester, transport, store, and release iron it can be speculated that tumor cells educate them to supply iron to support tumor growth. Recent evidence supports the existence of transferrin-independent iron transport mechanisms in the tumor microenvironment, which points to local iron transport proteins such as lipocalin-2 and/or low molecular weight iron-trafficking substances such as siderophores. We hypothesize that tumor cells educate immune cells, i.e. macrophages in their neighborhood to make them delivering iron for the benefit of cancer progression. In particular, we pay attention to recent developments, pointing to lipocalin-2 and siderophores as alternative iron transport molecules in the tumor microenvironment.