ArticleThe Journal of biological chemistry2014
Ovarian cancer cell heparan sulfate 6-O-sulfotransferases regulate an angiogenic program induced by heparin-binding epidermal growth factor (EGF)-like growth factor/EGF receptor signaling.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- The Human Ovary Exhibits Dynamic Molecular Remodeling in the Decades Post-Menopause.Aging cell · 2026Article
- Tumor promotion or suppression: Revisiting the role of EXT1 and Heparan sulfate.Histology and histopathology · 2026Review
- Glycan diversity in ovarian cancer: Unraveling the immune interplay and therapeutic prospects.Seminars in immunopathology · 2024Review
- Heparan sulfate 6-O-sulfotransferase 2 promotes gastric cancer progression by modulating the TGF-β/smad2/3 pathway.American journal of translational research · 2024Article
- Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance.American journal of translational research · 2024Article
- Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance.Scientific reports · 2023Article
- Role of Syndecans in Ovarian Cancer: New Diagnostic and Prognostic Biomarkers and Potential Therapeutic Targets.Cancers · 2023Review
- HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease.International journal of molecular sciences · 2023Review
- Phytochemical Profiling, Isolation, and Pharmacological Applications of Bioactive Compounds from Insects of the Family Blattidae Together with Related Drug Development.Molecules (Basel, Switzerland) · 2022Review
- The Extracellular Matrix of Articular Cartilage Controls the Bioavailability of Pericellular Matrix-Bound Growth Factors to Drive Tissue Homeostasis and Repair.International journal of molecular sciences · 2022Review
- Identification of a gene signature for the prediction of recurrence and progression in non-muscle-invasive bladder cancer.Molecular biomedicine · 2022Article
- Clinicopathological and Molecular Prognostic Classifier for Intermediate/High-Risk Clear Cell Renal Cell Carcinoma.Cancers · 2021Article
- Coxsackievirus B3-Its Potential as an Oncolytic Virus.Viruses · 2021Review
- Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management.Biomolecules · 2021Review
- Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression.Frontiers in oncology · 2021Review
- Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice.Discover oncology · 2021Article
- Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment.International journal of molecular sciences · 2020Review
- Selectins: An Important Family of Glycan-Binding Cell Adhesion Molecules in Ovarian Cancer.Cancers · 2020Review
- Tumor Microenvironment-Associated Extracellular Matrix Components Regulate NK Cell Function.Frontiers in immunology · 2020Review
- The Role of Proteoglycans in Cancer Metastasis and Circulating Tumor Cell Analysis.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparan sulfate (HS) is a component of cell surface and extracellular matrix proteoglycans that regulates numerous signaling pathways by binding and activating multiple growth factors and chemokines. The amount and pattern of HS sulfation are key determinants for the assembly of the trimolecular, HS-growth factor-receptor, signaling complex. Here we demonstrate that HS 6-O-sulfotransferases 1 and 2 (HS6ST-1 and HS6ST-2), which perform sulfation at 6-O position in glucosamine in HS, impact ovarian cancer angiogenesis through the HS-dependent HB-EGF/EGFR axis that subsequently modulates the expression of multiple angiogenic cytokines. Down-regulation of HS6ST-1 or HS6ST-2 in human ovarian cancer cell lines results in 30-50% reduction in glucosamine 6-O-sulfate levels in HS, impairing HB-EGF-dependent EGFR signaling and diminishing FGF2, IL-6, and IL-8 mRNA and protein levels in cancer cells. These cancer cell-related changes reduce endothelial cell signaling and tubule formation in vitro. In vivo, the development of subcutaneous tumor nodules with reduced 6-O-sulfation is significantly delayed at the initial stages of tumor establishment with further reduction in angiogenesis occurring throughout tumor growth. Our results show that in addition to the critical role that 6-O-sulfate moieties play in angiogenic cytokine activation, HS 6-O-sulfation level, determined by the expression of HS6ST isoforms in ovarian cancer cells, is a major regulator of angiogenic program in ovarian cancer cells impacting HB-EGF signaling and subsequent expression of angiogenic cytokines by cancer cells.
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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.