ArticleCell death discovery2025
SPON2 facilitates osteosarcoma development by inducing M2 macrophage polarization through activation of the NF-κB/VEGF signaling axis.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Targeting CD3L1-NRP2 disarms myeloid-driven tumor immune evasion.EMBO molecular medicine · 2026Article
- LncRNA GAS5 inhibits the remodeling of the tumor microenvironment by binding to miR-93-5p, thereby suppressing the development of osteosarcoma.Journal of orthopaedic surgery and research · 2026Article
- Article
- Nanoparticle-based mechanistic and multifunctional strategies for targeted osteosarcoma therapy.Discover nano · 2026Review
- Macrophage-centered immunotherapy for osteosarcoma: mechanisms, repolarization, and translational strategies.World journal of surgical oncology · 2026Review
- Deciphering stromal cell interactions in osteosarcoma highlights CDKN2A and MMP14 as novel diagnostic and therapeutic biomarkers.European journal of medical research · 2026Article
- Deciphering the malignant synergy: metabolic reprogramming, epigenetic circuitry, and niche remodeling in osteosarcoma-macrophage crosstalk.Frontiers in immunology · 2026Review
- Elevated cytokines in osteoporotic blood correlate with immune microenvironment shifts and dysregulated circRNA profiles.Frontiers in immunology · 2026Article
- Advances in the association between tumor immune microenvironment remodeling in osteosarcoma and the risk of pathological fractures.Frontiers in genetics · 2026Review
- Intelligent Nanomedicine Systems Utilizing Diverse Nanoparticles for Osteosarcoma Therapy: A Review.International journal of nanomedicine · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Osteosarcoma (OS) is an aggressive bone tumor with poor prognosis, particularly in metastatic cases. Here, we identify spondin 2 (SPON2) as a key driver of OS progression. SPON2 is significantly upregulated in OS tissues and cell lines and correlates with shorter patient survival. Functional assays show that SPON2 promotes OS cell proliferation, migration, invasion, and angiogenesis by enhancing the secretion of IL10, CCL2, and CSF1, which leads to M2 macrophage polarization and an immunosuppressive tumor microenvironment. In vitro, SPON2 knockdown reduces M2 macrophage markers and attenuates EMT phenotypes, as evidenced by decreased mesenchymal markers and preserved epithelial characteristics. Mechanistically, SPON2 activates the NF-κB/VEGF signaling axis to drive both macrophage polarization and EMT, thereby promoting tumor progression. In vivo, SPON2 knockdown in OS xenografts suppresses tumor growth, lung metastasis, and M2 polarization, while increasing M1-associated markers. Lipopolysaccharide (LPS) stimulation restores cytokine secretion and EMT marker expression in SPON2-knockdown models, suggesting that SPON2 acts through inflammation-responsive pathways. Together, these findings establish SPON2 as a key regulator of both immune modulation and metastatic behavior in OS, and highlight its potential as a therapeutic target.
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.