Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion

In this study, we use liquid chromatography–mass spectrometry analysis to demonstrate differences in HS disaccharide content and structure across four patient-derived tumorsphere lines (GBM1, 5, 6, 43) and between two murine tumorsphere lines derived from murine GBM with enrichment of mesenchymal and proneural gene expression (mMES and mPN, respectively) markers. In GBM, the heterogeneous HS content and structure across patient-derived tumorsphere lines suggested diverse functions in the GBM tumor microenvironment. In GBM5 and mPN, elevated expression of sulfatase 2 (SULF2), an extracellular enzyme that alters ligand binding to HS, was associated with low trisulfated HS disaccharides, a substrate of SULF2. In contrast, other primary tumorsphere lines had elevated expression of the HS-modifying enzyme heparanase (HPSE). Using gene editing strategies to inhibit HPSE, a role for HPSE in promoting tumor cell adhesion and invasion was identified. These studies characterize the heterogeneity in HS glycosaminoglycan content and structure across GBM and reveal their role in tumor cell invasion. Implications: HS-interacting factors promote GBM invasion and are potential therapeutic targets. Mol Cancer Res; 15(11); 1623–33. ©2017 AACR.
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signal Transduction Source Type: research

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Source: Methods - Category: Molecular Biology Source Type: research
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Source: Clinical Trials And Noteworthy Treatments For Brain Tumors - Category: Cancer & Oncology Source Type: clinical trials
Source: Clinical Trials And Noteworthy Treatments For Brain Tumors - Category: Cancer & Oncology Source Type: clinical trials
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Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research
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Source: Acta Neuropathologica - Category: Neurology Source Type: research
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Source: WebMD Health - Category: Consumer Health News Source Type: news
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Source: Archives of Pharmacal Research - Category: Drugs & Pharmacology Authors: Tags: Arch Pharm Res Source Type: research
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Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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