ArticleCell death & disease2019
TLR4 signaling drives mesenchymal stromal cells commitment to promote tumor microenvironment transformation in multiple myeloma.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Mitochondrial transfer-mediated metabolic reprogramming and drug resistance in bone metastasis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- The paracrine effects of tumor-resident mesenchymal stem/stromal cells in the microenvironment of brain metastases.Frontiers in oncology · 2026Article
- Circulating extracellular vesicle isomiR signatures predict therapy response in patients with multiple myeloma.Cell reports. Medicine · 2025Article
- Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma.Journal of translational medicine · 2025Article
- NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses.Scientific reports · 2025Article
- Mesenchymal stem cells as future treatment for cardiovascular regeneration and its challenges.Annals of translational medicine · 2024Review
- Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma.Blood advances · 2024Article
- An IL-1β-driven neutrophil-stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma.Nature immunology · 2024Article
- Hydrophobic Components in Light-Yellow Pulp Sweet Potato (Nutrients · 2024Article
- (+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease.Journal of translational medicine · 2024Article
- Anti-tumorigenic effects of naive and TLR4-primed adipose-derived mesenchymal stem cells on pancreatic ductal adenocarcinoma cells.Cancer medicine · 2024Article
- Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers.Biomolecules · 2023Review
- Modeling cell populations metabolism and competition under maximum power constraints.PLoS computational biology · 2023Article
- MacroH2A1.1 as a crossroad between epigenetics, inflammation and metabolism of mesenchymal stromal cells in myelodysplastic syndromes.Cell death & disease · 2023Article
- Role of NF-κB Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Review
- Metabolic Signature of Energy Metabolism Alterations and Excess Nitric Oxide Production in Culture Media Correlate with Low Human Embryo Quality and Unsuccessful Pregnancy.International journal of molecular sciences · 2023Article
- Shedding light on the molecular and regulatory mechanisms of TLR4 signaling in endothelial cells under physiological and inflamed conditions.Frontiers in immunology · 2023Review
- Mesenchymal stromal cells in tumor microenvironment remodeling of BCR-ABL negative myeloproliferative diseases.Frontiers in oncology · 2023Review
- Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance.Journal of clinical medicine · 2022Review
- Oct4 cooperates with c-Myc to improve mesenchymal-to-endothelial transition and myocardial repair of cardiac-resident mesenchymal stem cells.Stem cell research & therapy · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation represents a key feature and hallmark of tumor microenvironment playing a major role in the interaction with mesenchymal stromal cells (MSC) in cancer progression. The aim of the present study was to investigate the crosstalk between MSCs and myeloma cells (MM) in the pro-inflammatory microenvironment promoting immune evasion and tumor growth. MSC were collected from patients with diagnosis of MGUS (n = 10), smoldering myeloma (n = 7), multiple myeloma at diagnosis (n = 16), relapse (n = 5) or refractory (n = 3), and from age-matched healthy controls (HC, n = 10) and cultured with peripheral blood mononucleated cells (PBMC) from healthy volunteer donors. Similarly to MM, we showed that MSC from smoldering multiple myeloma (SMM) patients activated neutrophils and conferred an immunosuppressive and pro-angiogenic phenotype. Furthermore, co-cultures of plasma cells (PC) and HC-MSC suggested that such activation is driven by MM cells through the switching into a pro-inflammatory phenotype mediated by toll-like receptor 4 (TLR4). These results were further confirmed using a zebrafish as an immunocompetent in vivo model, showing the role of MM-MSC in supporting PCs engraftment and Th2 response. Such effect was abolished following inhibition of TLR4 signaling in MM-MSC before co-injection with PC. Moreover, the addition of a TLR4 inhibitor in the co-culture of HC-MSC with MM cells prevented the activation of the pro-tumor activity in PC-educated MSC. In conclusion, our study provides evidence that TLR4 signaling plays a key role in MSC transformation by inducing a pro-tumor phenotype associated with a permissive microenvironment allowing immune escape and tumor growth.
Identifiers
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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.