ArticleThe Journal of clinical investigation2014
Stromal heparan sulfate differentiates neuroblasts to suppress neuroblastoma growth.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 34 citations in OpenAlex.
- Emerging Role, Molecular Mechanisms, and Therapeutic Potential of 2-O, 3-O Desulfated Heparin (ODSH) Across Inflammatory and Vascular Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Diffuse hemispheric glioma, H3 G34-mutant, in Simpson-Golabi-Behmel syndrome: the first reported case.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Targeting the heparan sulfate proteoglycan/heparanase axis as a novel therapeutic strategy to drive adipogenesis and block tumor growth of dedifferentiated liposarcoma.International journal of biological sciences · 2026Article
- 1,4-Dioxane Induces Epithelial-Mesenchymal Transition and Carcinogenesis in an Nrf2-Dependent Manner.Journal of extracellular vesicles · 2025Article
- Bispecific GPC3/PD‑1 CAR‑T cells for the treatment of HCC.International journal of oncology · 2023Article
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- Chemistry and Function of Glycosaminoglycans in the Nervous System.Advances in neurobiology · 2023Review
- Review
- Article
- Syndecan-4 as a Pathogenesis Factor and Therapeutic Target in Cancer.Biomolecules · 2021Review
- Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer.Disease markers · 2020Article
- Spotlight on the Transglutaminase 2-Heparan Sulfate Interaction.Medical sciences (Basel, Switzerland) · 2019Review
- Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors.Frontiers in oncology · 2019Review
- Suppressive effect of syndecan ectodomains and N-desulfated heparins on osteoclastogenesis via direct binding to macrophage-colony stimulating factor.Cell death & disease · 2018Article
- Dually modified transmembrane proteoglycans in development and disease.Cytokine & growth factor reviews · 2018Review
- Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression.Frontiers in endocrinology · 2018Review
- Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes.Oncotarget · 2017Article
- Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Heparan sulfate hexasaccharide selectively inhibits cancer stem cells self-renewal by activating p38 MAP kinase.Oncotarget · 2016Article
- Energy metabolism in neuroblastoma and Wilms tumor.Translational pediatrics · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroblastoma prognosis is dependent on both the differentiation state and stromal content of the tumor. Neuroblastoma tumor stroma is thought to suppress neuroblast growth via release of soluble differentiating factors. Here, we identified critical growth-limiting components of the differentiating stroma secretome and designed a potential therapeutic strategy based on their central mechanism of action. We demonstrated that expression of heparan sulfate proteoglycans (HSPGs), including TβRIII, GPC1, GPC3, SDC3, and SDC4, is low in neuroblasts and high in the Schwannian stroma. Evaluation of neuroblastoma patient microarray data revealed an association between TGFBR3, GPC1, and SDC3 expression and improved prognosis. Treatment of neuroblastoma cell lines with soluble HSPGs promoted neuroblast differentiation via FGFR1 and ERK phosphorylation, leading to upregulation of the transcription factor inhibitor of DNA binding 1 (ID1). HSPGs also enhanced FGF2-dependent differentiation, and the anticoagulant heparin had a similar effect, leading to decreased neuroblast proliferation. Dissection of individual sulfation sites identified 2-O, 3-O-desulfated heparin (ODSH) as a differentiating agent, and treatment of orthotopic xenograft models with ODSH suppressed tumor growth and metastasis without anticoagulation. These studies support heparan sulfate signaling intermediates as prognostic and therapeutic neuroblastoma biomarkers and demonstrate that tumor stroma biology can inform the design of targeted molecular therapeutics.
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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.