ArticleOncogene2018
TET2-dependent IL-6 induction mediated by the tumor microenvironment promotes tumor metastasis in osteosarcoma.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- TMEM205 promotes M2-like macrophage polarization and advances the progression of triple-negative breast cancer.Breast cancer research and treatment · 2026Article
- Osteosarcoma as a communication-driven disease: redefining tumor-bone signaling networks as therapeutic targets.Frontiers in oncology · 2026Review
- Single-Cell Analysis Clarifies Pathological Heterogeneity in Tenosynovial Giant Cell Tumor and Identifies Biomarkers for Predicting Disease Recurrence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Osteosarcoma Exosome Priming of Primary Human Lung Fibroblasts Induces an Immune Modulatory and Protumorigenic Phenotype.Cancer research communications · 2025Article
- TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Epigenetic Modifiers in Cancer Metastasis.Biomolecules · 2024Review
- AURKB promotes immunogenicity and immune infiltration in clear cell renal cell carcinoma.Discover oncology · 2024Article
- TET2 Is Downregulated in Early Esophageal Squamous Cell Carcinoma and Promotes Esophageal Squamous Cell Malignant Behaviors.Digestive diseases and sciences · 2024Article
- Exploration of anti‑osteosarcoma activity of asiatic acid based on network pharmacology andOncology reports · 2024Article
- Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations.Biomolecules · 2024Review
- Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.Frontiers in pharmacology · 2024Review
- ANGPTL2-mediated epigenetic repression of MHC-I in tumor cells accelerates tumor immune evasion.Molecular oncology · 2023Article
- The Role of Pyroptosis in the Pathogenesis of Kidney Diseases.Kidney diseases (Basel, Switzerland) · 2023Review
- DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development.Molecular genetics and genomics : MGG · 2023Article
- ITGB3 promotes cisplatin resistance in osteosarcoma tumors.Cancer medicine · 2023Article
- A novel anoikis-related gene signature to predict the prognosis, immune infiltration, and therapeutic outcome of lung adenocarcinoma.Journal of thoracic disease · 2023Article
- Exploring the key genetic association between chronic pancreatitis and pancreatic ductal adenocarcinoma through integrated bioinformatics.Frontiers in genetics · 2023Article
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
- Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma.Molecular therapy oncolytics · 2022Article
- Macrophage migration inhibitory factor is overproduced through EGR1 in TET2Communications biology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor microenvironment promotes epigenetic changes in tumor cells associated with tumor aggressiveness. Here we report that in primary tumor cells, increased interleukin-6 (IL-6) expression brought on by DNA demethylation of its promoter by ten-eleven translocation 2 (TET2) promotes lung metastasis in osteosarcoma (OS). Xenograft experiments show increased IL-6 expression and decreased methylation of its promoter in OS cells after implantation relative to before implantation. In addition, changes in IL-6 methylation and expression seen in OS cells at the primary site were maintained at the metastatic site. TET2 knockdown in OS cells suppressed upregulation of IL-6 and demethylation of its promoter in xenograft tumors and decreased tumor metastasis. We also present evidence showing that tumor cell-derived IL-6 facilitates glycolytic metabolism in tumor cells by activating the MEK/ERK1/2/hypoxia-inducible transcription factor-1α (HIF-1α) pathway and increases lung colonization by OS cells by upregulating expression of intercellular adhesion molecule-1 (ICAM-1), enhancing tumor metastasis. Blocking IL-6 signaling with a humanized monoclonal antibody against the IL-6 receptor reduced lung metastasis and prolonged survival of xenografted mice. These findings suggest that TET2-dependent IL-6 induction enables acquisition of aggressive phenotypes in OS cells via the tumor microenvironment and that blocking IL-6 signaling could be serve as a potential therapy to antagonize metastasis.
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