ArticleThe Journal of biological chemistry2008
Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
What it found
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The trial behind it
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Who cites it
113 citing papers in PubMed, 179 citations in OpenAlex.
- Priming of human monocytes by β-glucan and obesity-associated factors: modifications to global DNA methylation, gene expression, phenotype and function.Frontiers in immunology · 2026Article
- Role of the endothelial cell glycocalyx in sepsis-induced acute kidney injury.Frontiers in medicine · 2025Review
- Heparan sulfate chains in hepatocellular carcinoma.Gastroenterology report · 2025Review
- Targeted therapy for multiple myeloma: an overview on CD138-based strategies.Frontiers in oncology · 2024Review
- Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma.Cells · 2023Article
- Targeting syndecan-1: new opportunities in cancer therapy.American journal of physiology. Cell physiology · 2022Review
- Heparanase Blockade as a Novel Dual-Targeting Therapy for COVID-19.Journal of virology · 2022Article
- Unfractionated Heparin Attenuated Histone-Induced Pulmonary Syndecan-1 Degradation in Mice: a Preliminary Study on the Roles of Heparinase Pathway.Inflammation · 2022Article
- Heparanase 1 Upregulation Promotes Tumor Progression and Is a Predictor of Low Survival for Oral Cancer.Frontiers in cell and developmental biology · 2022Article
- Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma CellsFrontiers in oncology · 2022Article
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis.Marine drugs · 2021Article
- Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics.International journal of molecular sciences · 2021Article
- Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.Seminars in thrombosis and hemostasis · 2021Review
- The Role of Heparin and Glycocalyx in Blood-Brain Barrier Dysfunction.Frontiers in immunology · 2021Review
- Increased Plasma Heparanase Activity and Endothelial Glycocalyx Degradation in Dengue Patients Is Associated With Plasma Leakage.Frontiers in immunology · 2021Article
- Article
- Heparanase-enhanced Shedding of Syndecan-1 and Its Role in Driving Disease Pathogenesis and Progression.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Heparanase, cell signaling, and viral infections.Cellular and molecular life sciences : CMLS · 2020Review
- Emerging Role of Syndecans in Extracellular Matrix Remodeling in Cancer.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
High levels of heparanase are an indicator of poor prognosis in myeloma patients, and up-regulation of the enzyme enhances tumor growth, angiogenesis, and metastasis in animal models. At least part of the impact of heparanase in driving the aggressive tumor phenotype is due to its effect on increasing the expression and shedding of the heparan sulfate proteoglycan syndecan-1, a molecule known to promote myeloma progression. The present work demonstrated that elevation in heparanase expression in myeloma cells stimulates sustained ERK phosphorylation that in turn drives MMP-9 expression. In addition, urokinase-type plasminogen activator (uPA) and uPA receptor expression levels increased, and blocking the proteolytic activation of either MMP-9 or uPA inhibited the heparanase-induced increase in syndecan-1 shedding. Together these data provide a mechanism for heparanase-induced syndecan-1 shedding and, more importantly, demonstrate that heparanase activity in myeloma cells can lead to increased levels of proteases that are known to play important roles in the aggressive behavior of myeloma tumors. This in addition to its other known biological roles, indicates that heparanase acts as a master regulator of the aggressive tumor phenotype by up-regulating protease expression and activity within the tumor microenvironment.
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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.