ArticleJournal of bone oncology2015
RANK and RANK ligand expression in primary human osteosarcoma.
Article in Journal of bone oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pooled it
- A Phase 2 Trial of RANKL Antibody, Denosumab, in Two Cohorts of Patients with Recurrent/Refractory Osteosarcoma, a Report from the Children's Oncology Group.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Progress in immune microenvironment, immunotherapy and prognostic biomarkers in pediatric osteosarcoma.Frontiers in immunology · 2025Review
- Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition.International journal of molecular sciences · 2024Article
- The OSR9 Regimen: A New Augmentation Strategy for Osteosarcoma Treatment Using Nine Older Drugs from General Medicine to Inhibit Growth Drive.International journal of molecular sciences · 2023Review
- Advances in Osteosarcoma.Current osteoporosis reports · 2023Review
- Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.International journal of molecular sciences · 2023Review
- Review
- Comprehensive conservative treatment for multiple metastases of skull osteosarcoma: A case report.Frontiers in neurology · 2023Article
- The interaction between osteosarcoma and other cells in the bone microenvironment: From mechanism to clinical applications.Frontiers in cell and developmental biology · 2023Review
- Breast carcinomas with osteoclast-like giant cells: a comprehensive clinico-pathological and molecular portrait and evidence of RANK-L expression.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Osteosarcoma in Children: Not Only Chemotherapy.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Galangin suppresses RANKL-induced osteoclastogenesis via inhibiting MAPK and NF-κB signalling pathways.Journal of cellular and molecular medicine · 2021Article
- Evaluation of the Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) Expression in Osteosarcoma and Its Association with the Clinicopathological Data.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Article
- Review
- [Osteoid-forming bone tumors : Morphology and current translational cell biology].Der Pathologe · 2020Review
- Mifamurtide and TAM-like macrophages: effect on proliferation, migration and differentiation of osteosarcoma cells.Oncotarget · 2020Article
- Emerging Anticancer Potentials of Selenium on Osteosarcoma.International journal of molecular sciences · 2019Review
- Unusual Multinucleated Giant Cell Reaction in a Tongue Squamous Cell Carcinoma: Histopathological and Immunohistochemical Features.Head and neck pathology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor activator of nuclear factor kappa-B ligand (RANKL) is an essential mediator of osteoclast formation, function and survival. In patients with solid tumor metastasis to the bone, targeting the bone microenvironment by inhibition of RANKL using denosumab, a fully human monoclonal antibody (mAb) specific to RANKL, has been demonstrated to prevent tumor-induced osteolysis and subsequent skeletal complications. Recently, a prominent functional role for the RANKL pathway has emerged in the primary bone tumor giant cell tumor of bone (GCTB). Expression of both RANKL and RANK is extremely high in GCTB tumors and denosumab treatment was associated with tumor regression and reduced tumor-associated bone lysis in GCTB patients. In order to address the potential role of the RANKL pathway in another primary bone tumor, this study assessed human RANKL and RANK expression in human primary osteosarcoma (OS) using specific mAbs, validated and optimized for immunohistochemistry (IHC) or flow cytometry. Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79) of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor.
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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.