ArticleBMC cancer2022
MIF/CXCR4 signaling axis contributes to survival, invasion, and drug resistance of metastatic neuroblastoma cells in the bone marrow microenvironment.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Genome-wide association, single-cell, and spatial transcriptomics analyses reveal the role of the STK24-expressing positive cells in LUAD progression and the tumor microenvironment, identifying STK24 as a potential therapeutic target.Journal of translational medicine · 2025Article
- Myeloid-targeting immunotherapies overcome inhibitory barriers in immune-evasive neuroblastoma.The Journal of experimental medicine · 2025Article
- Distinct platelet transcriptomic heterogeneity in respiratory illnesses and modulation by corticosteroids and immune antibody treatments.Journal of translational medicine · 2025Article
- Flow Cytometry Multiplex Bead Array Technology and Its Immunological Clinical Applications in Covid-19 Era.Balkan journal of medical genetics : BJMG · 2025Article
- Machine learning-based integration reveals immunological heterogeneity and the clinical potential of T cell receptor (TCR) gene pattern in hepatocellular carcinoma.Apoptosis : an international journal on programmed cell death · 2025Article
- Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma.European journal of cancer (Oxford, England : 1990) · 2025Article
- Exosomal miRNA expression profiling in patients with imatinib resistant Chronic myeloid leukemia: A pilot study.PloS one · 2025Article
- Macrophage migration inhibitory factor (MIF) and the tumor ecosystem: a tale of inflammation, immune escape, and tumor growth.Frontiers in immunology · 2025Review
- The neuroblastoma tumor microenvironment: From an in-depth characterization towards novel therapies.EJC paediatric oncology · 2024Article
- Management of High-Risk Neuroblastoma with Soft-Tissue-Only Disease in the Era of Anti-GD2 Immunotherapy.Cancers · 2024Article
- Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia.Cell death discovery · 2024Article
- Revealing the role of SPP1Cell & bioscience · 2024Article
- Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.Frontiers in immunology · 2024Article
- Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023Review
- Exploring the Role of CD74 and D-Dopachrome Tautomerase in COVID-19: Insights from Transcriptomic and Serum Analyses.Journal of clinical medicine · 2023Article
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe bone marrow (BM) is the most common site of dissemination in patients with aggressive, metastatic neuroblastoma (NB). However, the molecular mechanisms underlying the aggressive behavior of NB cells in the BM niche are still greatly unknown. In the present study, we explored biological mechanisms that play a critical role in NB cell survival and progression in the BM and investigated potential therapeutic targets.
methodsPatient-derived bone marrow (BM) primary cultures were generated using fresh BM aspirates obtained from NB patients. NB cell lines were cultured in the presence of BM conditioned media containing cell-secreted factors, and under low oxygen levels (1% O
resultsWe identified macrophage migration inhibitory factor (MIF) as a key inflammatory cytokine involved in BM infiltration. Cytokine profiling and RNA-sequencing data analysis revealed NB cells as the main source of MIF in the BM, suggesting a potential role of MIF in tumor invasion. Exposure of NB cells to BM-conditions increased NB cell-surface expression of the MIF receptor CXCR4, which was associated with increased cell viability, enhanced migration-invasion, and activation of PI3K/AKT and MAPK/ERK signaling pathways. Moreover, subcutaneous co-injection of NB and BM cells enhanced tumor engraftment in mice. MIF inhibition with 4-IPP impaired in vitro NB aggressiveness, and improved drug response while delayed NB growth, improving survival of the NB xenograft model.
conclusionsOur findings suggest that BM infiltration by NB cells may be mediated, in part, by MIF-CXCR4 signaling. We demonstrate the antitumor efficacy of MIF targeting in vitro and in vivo that could represent a novel therapeutic target for patients with disseminated high-risk NB.
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