ArticleBMC cancer2010
Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.
Article in BMC cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Chromosomal 3p loss and 8q gain drive vasculogenic mimicry via HIF-2α and VE-cadherin activation in uveal melanoma.Cell death and differentiation · 2025Article
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- Regulation of Metastasis in Ewing Sarcoma.Cancers · 2022Review
- Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma.Nature communications · 2022Article
- Article
- The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review.Frontiers in oncology · 2022Review
- A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma.Frontiers in genetics · 2022Article
- The Landscape of Regulatory Noncoding RNAs in Ewing's Sarcoma.Biomedicines · 2021Review
- Characterization of bony anatomic regions in pediatric and adult healthy volunteers using diffuse optical spectroscopic imaging.Journal of biomedical optics · 2020Article
- Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways.Cancer letters · 2020Article
- Microvesicles derived from human bone marrow mesenchymal stem cells promote U2OS cell growth under hypoxia: the role of PI3K/AKT and HIF-1α.Human cell · 2019Article
- EWS-FLI1 reprograms the metabolism of Ewing sarcoma cells via positive regulation of glutamine import and serine-glycine biosynthesis.Molecular carcinogenesis · 2018Article
- Angiopoietin-like 4 promotes osteosarcoma cell proliferation and migration and stimulates osteoclastogenesis.BMC cancer · 2018Article
- Established Models and New Paradigms for Hypoxia-Driven Cancer-Associated Bone Disease.Calcified tissue international · 2018Review
- EZH2, HIF-1, and Their Inhibitors: An Overview on Pediatric Cancers.Frontiers in pediatrics · 2018Review
- Metabolic modulation of Ewing sarcoma cells inhibits tumor growth and stem cell properties.Oncotarget · 2017Article
- HIF-2α affects proliferation and apoptosis of MG-63 osteosarcoma cells through MAPK signaling.Molecular medicine reports · 2017Article
- In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis.Journal of visualized experiments : JoVE · 2016Article
- Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology.Neuropeptides · 2016Review
- Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma.
methodsHIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration.
results17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration.
conclusionsCo-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.
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