ArticleThe Journal of clinical investigation2012
Heparan sulfate sulfatase SULF2 regulates PDGFRα signaling and growth in human and mouse malignant glioma.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 99 citations in OpenAlex.
- A non-canonical EZH2/TRIM28 epigenetic axis drives heparan sulfate remodeling and melanoma metastasis.bioRxiv : the preprint server for biology · 2026Article
- Murine vascular organoids are responsive and adaptable 3D systems with cellular heterogeneity and dynamic plasticity.Science advances · 2025Article
- Elucidating the multifaceted role and therapeutic potential of Sulf-2 in human tumor biology.Biomarkers in medicine · 2025Review
- Editor's Choice Development of a method to measure the activity of heparan sulfate 6-endosulfatase for biological research.Glycobiology · 2025Article
- Construction of an Extracellular Matrix-Related Risk Model to Analyze the Correlation Between Glioblastoma and Tumor Immunity.BioMed research international · 2025Article
- A novel risk model consisting of nine platelet-related gene signatures for predicting prognosis, immune features and drug sensitivity in glioma.Hereditas · 2024Article
- The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer.Breast cancer research : BCR · 2024Article
- Integrating Machine Learning and Mendelian Randomization Determined a Functional Neurotrophin-Related Gene Signature in Patients with Lower-Grade Glioma.Molecular biotechnology · 2024Article
- 6-O-endosulfatases in tumor metastasis: heparan sulfate proteoglycans modification and potential therapeutic targets.American journal of cancer research · 2024Review
- Heparan-6-Cancers · 2023Article
- LIN28B and Let-7 in Diffuse Midline Glioma: A Review.Cancers · 2023Review
- Molecular subtypes based on PANoptosis-related genes and tumor microenvironment infiltration characteristics in lower-grade glioma.Functional & integrative genomics · 2023Review
- In-Depth Matrisome and Glycoproteomic Analysis of Human Brain Glioblastoma Versus Control Tissue.Molecular & cellular proteomics : MCP · 2022Article
- Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma.Advanced healthcare materials · 2022Review
- Measuring Sulfatase Expression and Invasion in Glioblastoma.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination.Nature communications · 2021Article
- Synthesis and Screening of α-Xylosides in Human Glioblastoma Cells.Molecular pharmaceutics · 2021Article
- Heparan Sulfate Synthesized byMolecular cancer research : MCR · 2021Article
- Concepts of extracellular matrix remodelling in tumour progression and metastasis.Nature communications · 2020Review
- Chondroitin sulfate synthase 1 enhances proliferation of glioblastoma by modulating PDGFRA stability.Oncogenesis · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Glioblastoma (GBM), a uniformly lethal brain cancer, is characterized by diffuse invasion and abnormal activation of multiple receptor tyrosine kinase (RTK) signaling pathways, presenting a major challenge to effective therapy. The activation of many RTK pathways is regulated by extracellular heparan sulfate proteoglycans (HSPG), suggesting these molecules may be effective targets in the tumor microenvironment. In this study, we demonstrated that the extracellular sulfatase, SULF2, an enzyme that regulates multiple HSPG-dependent RTK signaling pathways, was expressed in primary human GBM tumors and cell lines. Knockdown of SULF2 in human GBM cell lines and generation of gliomas from Sulf2(-/-) tumorigenic neurospheres resulted in decreased growth in vivo in mice. We found a striking SULF2 dependence in activity of PDGFRα, a major signaling pathway in GBM. Ablation of SULF2 resulted in decreased PDGFRα phosphorylation and decreased downstream MAPK signaling activity. Interestingly, in a survey of SULF2 levels in different subtypes of GBM, the proneural subtype, characterized by aberrations in PDGFRα, demonstrated the strongest SULF2 expression. Therefore, in addition to its potential as an upstream target for therapy of GBM, SULF2 may help identify a subset of GBMs that are more dependent on exogenous growth factor-mediated signaling. Our results suggest the bioavailability of growth factors from the microenvironment is a significant contributor to tumor growth in a major subset of human GBM.
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Registered trials
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