ArticleThe American journal of pathology2016
Inhibition of Transforming Growth Factor-β Activation Diminishes Tumor Progression and Osteolytic Bone Disease in Mouse Models of Multiple Myeloma.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Malignant transformation in patients with monoclonal gammopathy of undetermined significance treated with teriparatide for osteoporosis: a bicenter retrospective study and analysis of the French national pharmacovigilance database.Archives of osteoporosis · 2026Observational
- TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis.Cell death & disease · 2026Article
- Comprehensive Bioinformatic Analysis Reveals Survival-Associated Hub Genes and MicroRNAs in Multiple Myeloma Patients.Iranian journal of biotechnology · 2025Article
- Dose-Dependent Effects of TGF-β Inhibition on Osteoblast Differentiation and Wound Healing.Current issues in molecular biology · 2025Article
- Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.Journal of bone oncology · 2025Review
- Burden of multiple myeloma in Asian countries from 1990 to 2021 and trend prediction for 2050: an analysis based on the Global Burden of Disease Study 2021.Frontiers in medicine · 2025Article
- THBS1 mediates hypoxia driven EndMT in pulmonary hypertension.Pulmonary circulation · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Increased thrombospondin-1 levels contribute to epileptic susceptibility in neonatal hyperthermia without seizures via altered synaptogenesis.Cell death discovery · 2024Article
- Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment.Frontiers in oncology · 2023Article
- A novel immunogenic cell death signature for the prediction of prognosis and therapies in glioma.PeerJ · 2023Article
- CXCL13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression.Journal of hematology & oncology · 2022Article
- Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma.Cancers · 2022Review
- Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma.Journal of hematology & oncology · 2022Review
- Runx2 Deficiency in Osteoblasts Promotes Myeloma Resistance to Bortezomib by Increasing TSP-1-Dependent TGFβ1 Activation and Suppressing Immunity in Bone Marrow.Molecular cancer therapeutics · 2022Article
- Review
- The yin-yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma.Frontiers in immunology · 2022Review
- Myeloma Bone Disease: The Osteoblast in the Spotlight.Journal of clinical medicine · 2021Review
- Myeloma Bone Disease: A Comprehensive Review.International journal of molecular sciences · 2021Review
- TAK1 is a pivotal therapeutic target for tumor progression and bone destruction in myeloma.Haematologica · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Transforming growth factor (TGF)-β supports multiple myeloma progression and associated osteolytic bone disease. Conversion of latent TGF-β to its biologically active form is a major regulatory node controlling its activity. Thrombospondin1 (TSP1) binds and activates TGF-β. TSP1 is increased in myeloma, and TSP1-TGF-β activation inhibits osteoblast differentiation. We hypothesized that TSP1 regulates TGF-β activity in myeloma and that antagonism of the TSP1-TGF-β axis inhibits myeloma progression. Antagonists (LSKL peptide, SRI31277) derived from the LSKL sequence of latent TGF-β that block TSP1-TGF-β activation were used to determine the role of the TSP1-TGF-β pathway in mouse models of myeloma. TSP1 binds to human myeloma cells and activates TGF-β produced by cultured human and mouse myeloma cell lines. Antagonists delivered via osmotic pump in an intratibial severe combined immunodeficiency CAG myeloma model or in a systemic severe combined immunodeficiency CAG-heparanase model of aggressive myeloma reduced TGF-β signaling (phospho-Smad 2) in bone sections, tumor burden, mouse IL-6, and osteoclasts, increased osteoblast number, and inhibited bone destruction as measured by microcomputed tomography. SRI31277 reduced tumor burden in the immune competent 5TGM1 myeloma model. SRI31277 was as effective as dexamethasone or bortezomib, and SRI31277 combined with bortezomib showed greater tumor reduction than either agent alone. These studies validate TSP1-regulated TGF-β activation as a therapeutic strategy for targeted inhibition of TGF-β in myeloma.
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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.