ArticleJCI insight2018
IL-6 and CXCL8 mediate osteosarcoma-lung interactions critical to metastasis.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed, 78 citations in OpenAlex.
- [Parecoxib sodium down-regulates CXCL8-CXCR1/2 to improve inflammatory microenvironment and promote patient recovery following laparoscopic radical resection of rectal cancer].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Trial
- Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8.Science advances · 2022Trial
- IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets.Immunology · 2026Review
- Sarcoma metastasis: distinct biological principles beyond the carcinoma paradigm.Cancer metastasis reviews · 2026Review
- Understanding and Overcoming Osteosarcoma Heterogeneity.Biomolecules · 2026Review
- Decoding CTCs in osteosarcoma: the molecular journey from initial tumor to metastasis.Scientific reports · 2026Article
- Osteosarcoma as a communication-driven disease: redefining tumor-bone signaling networks as therapeutic targets.Frontiers in oncology · 2026Review
- Metastasis-Initiating Osteosarcoma Subpopulations Establish Paracrine Interactions with Lung and Tumor Cells to Create a Metastatic Niche.Cancer research · 2025Article
- Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages.Cancer immunology, immunotherapy : CII · 2025Article
- Osteosarcoma Exosome Priming of Primary Human Lung Fibroblasts Induces an Immune Modulatory and Protumorigenic Phenotype.Cancer research communications · 2025Article
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Aberrant Activation of Wound-Healing Programs within the Metastatic Niche Facilitates Lung Colonization by Osteosarcoma Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- STAT3 inhibition in combination with CD47 blockade inhibits osteosarcoma lung metastasis.Frontiers in immunology · 2025Article
- Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma.Molecular therapy. Oncology · 2024Article
- Osteosarcoma through the Lens of Bone Development, Signaling, and Microenvironment.Cold Spring Harbor perspectives in medicine · 2024Review
- Directing B7-H3 chimeric antigen receptor T cell homing through IL-8 induces potent antitumor activity against pediatric sarcoma.Journal for immunotherapy of cancer · 2024Article
- Review
- Advances in prognostic models for osteosarcoma risk.Heliyon · 2024Review
- Single‑agent nintedanib suppresses metastatic osteosarcoma growth by inhibiting tumor vascular formation.Oncology letters · 2024Article
- Pivotal role of IL-8 derived from the interaction between osteosarcoma and tumor-associated macrophages in osteosarcoma growth and metastasis via the FAK pathway.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Osteosarcoma (OS), a malignant tumor of bone, kills through aggressive metastatic spread almost exclusively to the lung. Mechanisms driving this tropism for lung tissue remain unknown, though likely invoke specific interactions between tumor cells and other cells within the lung metastatic niche. Aberrant overexpression of ΔNp63 in OS cells directly drives production of IL-6 and CXCL8. All these factors were expressed at higher levels in OS lung metastases than in matched primary tumors from the same patients. Expression in cell lines correlated strongly with lung colonization efficiency in murine xenograft models. Lentivirus-mediated expression endowed poorly metastatic OS cells with increased metastatic capacity. Disruption of IL-6 and CXCL8 signaling using genetic or pharmaceutical inhibitors had minimal effects on tumor cell proliferation in vitro or in vivo, but combination treatment inhibited metastasis across multiple models of metastatic OS. Strong interactions occurred between OS cells and both primary bronchial epithelial cells and bronchial smooth muscle cells that drove feed-forward amplification of IL-6 and CXCL8 production. These results identify IL-6 and CXCL8 as primary mediators of OS lung tropism and suggest pleiotropic, redundant mechanisms by which they might effect metastasis. Combination therapy studies demonstrate proof of concept for targeting these tumor-lung interactions to affect metastatic disease.
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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.