ArticlePloS one2016
Intracellular Iron Chelation Modulates the Macrophage Iron Phenotype with Consequences on Tumor Progression.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 81 citations in OpenAlex.
- Discovery of ALA-hydroxypyridinone hybrids: novel strategies for photodynamic therapy against superficial tumours.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Neonatal monocyte iron metabolism and immunometabolic responses in sepsis: a comparative ex vivo investigation.Pediatric research · 2026Article
- Prochelators modulate azole activity againstRSC chemical biology · 2026Article
- Review
- Asbestos Disease Initiation.Bulletin of mathematical biology · 2026Article
- Iron and metabolic rewiring in cancer.Oncogenesis · 2026Review
- Natural extract-derived compounds for the treatment of hematological diseases through modulation of the bone marrow microenvironment.Frontiers in chemistry · 2026Review
- Metal homeostasis as a therapeutic lever: advancing metalloimmunology to remodel the tumor microenvironment and enhance cancer immunotherapy.Theranostics · 2026Review
- Assessment of the Impact of Trace Essential Metals on Cancer Development.International journal of molecular sciences · 2024Review
- Quinoline-based tetrazolium prochelators: formazan release, iron sequestration, and antiproliferative efficacy in cancer cells.Chemical communications (Cambridge, England) · 2024Article
- A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron.Nature immunology · 2024Article
- Harnessing innate immune pathways for therapeutic advancement in cancer.Signal transduction and targeted therapy · 2024Review
- Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.Frontiers in immunology · 2024Review
- A new perspective on the therapeutic potential of tumor metastasis: targeting the metabolic interactions between TAMs and tumor cells.International journal of biological sciences · 2024Review
- The role of the C5a-C5aR pathway in iron metabolism and gastric cancer progression.Frontiers in immunology · 2024Article
- Advances in macrophage and T cell metabolic reprogramming and immunotherapy in the tumor microenvironment.PeerJ · 2024Article
- Macrophage metabolism, phenotype, function, and therapy in hepatocellular carcinoma (HCC).Journal of translational medicine · 2023Review
- Design of Tetrazolium Cations for the Release of Antiproliferative Formazan Chelators in Mammalian Cells.Journal of the American Chemical Society · 2023Article
- Review
- Targeting iron to contrast cancer progression.Current opinion in chemical biology · 2023Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A growing body of evidence suggests that macrophage polarization dictates the expression of iron-regulated genes. Polarization towards iron sequestration depletes the microenvironment, whereby extracellular pathogen growth is limited and inflammation is fostered. In contrast, iron release contributes to cell proliferation, which is important for tissue regeneration. Moreover, macrophages constitute a major component of the infiltrates in most solid tumors. Considering the pivotal role of macrophages for iron homeostasis and their presence in association with poor clinical prognosis in tumors, we approached the possibility to target macrophages with intracellular iron chelators. Analyzing the expression of iron-regulated genes at mRNA and protein level in primary human macrophages, we found that the iron-release phenotype is a characteristic of polarized macrophages that, in turn, stimulate tumor cell growth and progression. The application of the intracellular iron chelator (TC3-S)2 shifted the macrophage phenotype from iron release towards sequestration, as determined by the iron-gene profile and atomic absorption spectroscopy (AAS). Moreover, whereas the addition of macrophage supernatants to tumor cells induced tumor growth and metastatic behavior, the supernatant of chelator-treated macrophages reversed this effect. Iron chelators demonstrated potent anti-neoplastic properties in a number of cancers, both in cell culture and in clinical trials. Our results suggest that iron chelation could affect not only cancer cells but also the tumor microenvironment by altering the iron-release phenotype of tumor-associated macrophages (TAMs). The study of iron chelators in conjunction with the effect of TAMs on tumor growth could lead to an improved understanding of the role of iron in cancer biology and to novel therapeutic avenues for iron chelation approaches.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.