ArticleMatrix biology : journal of the International Society for Matrix Biology2016
Chemotherapy induces expression and release of heparanase leading to changes associated with an aggressive tumor phenotype.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 82 citations in OpenAlex.
- Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study.Medical gas researchTrial
- Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application.Bioactive materials · 2026Review
- Heparanase (HPSE) genetic variants as prognostic indicators in ovarian cancer: evidence from discovery and validation cohorts.Molecular biology reports · 2026Article
- The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Could Hydrophobicity of Sulfated Pseudo-Trisaccharides Derived from Repurposing Aminoglycoside Tobramycin Modulate the Enzymatic Activity of Heparanase?Journal of medicinal chemistry · 2025Article
- Design of Paromomycin and Neomycin as Sulfated and Hydrophobic Glycans to Target Heparanase-Driven Tumor Progression and Metastasis.Journal of medicinal chemistry · 2025Article
- The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer.Breast cancer research : BCR · 2024Article
- Hypoxia-induced activation of HIF-1alpha/IL-1beta axis in microglia promotes glioma progression via NF-κB-mediated upregulation of heparanase expression.Biology direct · 2024Article
- Exosomes biogenesis was increased in metformin-treated human ovary cancer cells; possibly to mediate resistance.Cancer cell international · 2024Article
- Proteomic analysis reveals key differences in pro-stromal corneal tissue between highly myopic males and females.Frontiers in medicine · 2024Article
- Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma.Cells · 2023Article
- Heparanase Modulates Chromatin Accessibility.Cells · 2023Article
- Extracellular vesicles released during hypoxia transport heparanase and enhance macrophage migration, endothelial tube formation and cancer cell stemness.Proteoglycan research · 2023Article
- Protectin DX Relieve Hyperoxia-induced Lung Injury by Protecting Pulmonary Endothelial Glycocalyx.Journal of inflammation research · 2023Article
- A positive feedback loop of heparanase/syndecan1/nerve growth factor regulates cancer pain progression.The Korean journal of pain · 2023Article
- A 3D, Compartmental Tumor-Stromal Microenvironment Model of Patient-Derived Bone Metastasis.International journal of molecular sciences · 2022Article
- Induction of heparanase 2 (Hpa2) expression by stress is mediated by ATF3.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis.Respiratory research · 2021Article
- Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study.Journal of clinical medicine · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
High heparanase expression is associated with enhanced tumor growth, angiogenesis, and metastasis in many types of cancer. However, the mechanisms driving high heparanase expression are not fully understood. In the present study, we discovered that drugs used in the treatment of myeloma upregulate heparanase expression. Frontline anti-myeloma drugs, bortezomib and carfilzomib activate the nuclear factor-kappa B (NF-κB) pathway to trigger heparanase expression in tumor cells. Blocking the NF-κB pathway diminished this chemotherapy-induced upregulation of heparanase expression. Activated NF-κB signaling was also found to drive high heparanase expression in drug resistant myeloma cell lines. In addition to enhancing heparanase expression, chemotherapy also caused release of heparanase by tumor cells into the conditioned medium. This soluble heparanase was taken up by macrophages and triggered an increase in TNF-α production. Heparanase is also taken up by tumor cells where it induced expression of HGF, VEGF and MMP-9 and activated ERK and Akt signaling pathways. These changes induced by heparanase are known to be associated with the promotion of an aggressive tumor phenotype. Importantly, the heparanase inhibitor Roneparstat diminished the uptake and the downstream effects of soluble heparanase. Together, these discoveries reveal a novel mechanism whereby chemotherapy upregulates heparanase, a known promoter of myeloma growth, and suggest that therapeutic targeting of heparanase during anti-cancer therapy may improve patient outcome.
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Registered trials
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