Cited by 189Proteoglycans and glycosaminoglycans researchProtease and Inhibitor MechanismsTGF-β signaling in diseases

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The heparanase/syndecan‐1 axis in cancer: mechanisms and therapies

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Ramani, Vishnu C., Purushothaman, Anurag, Stewart, Mark D., Thompson, Camilla A., Vlodavsky, Israel, Au, Jessie L‐S., Sanderson, Ralph D.·2013·The FEBS Journal

DOI 10.1111/febs.12168PMC PMC3651779

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Abstract

Heparanase is an endoglucuronidase that cleaves heparan sulfate chains of proteoglycans. In many malignancies, high heparanase expression and activity correlate with an aggressive tumour phenotype. A major consequence of heparanase action in cancer is a robust up‐regulation of growth factor expression and increased shedding of syndecan‐1 (a transmembrane heparan sulfate proteoglycan). Substantial evidence indicates that heparanase and syndecan‐1 work together to drive growth factor signalling and regulate cell behaviours that enhance tumour growth, dissemination, angiogenesis and osteolysis. Preclinical and clinical studies have demonstrated that therapies targeting the heparanase/syndecan‐1 axis hold promise for blocking the aggressive behaviour of cancer.

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10.1042/0264-6021:3370471 · DOI

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Extracellular matrix structure
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“A number of preclinical and clinical findings have reported that targeting pathways and molecules involved in the formation of exosome can inhibit tumor progression, such as heparanase/syndecan-1 axis [182, 183] or syndecan heparan sulfate proteoglycans [179, 184] .”
Background
Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments
Yuan, Z., Li, Y., Zhang, S., Wang, X., Dou, H., Yu, X., Zhang, Z., Yang, S., & Xiao, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01744-8 · Cited by 977
Exosome-Mediated Metastasis: From Epithelial–Mesenchymal Transition to Escape from Immunosurveillance
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TIMPs: versatile extracellular regulators in cancer
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See all 189

Authors: Ramani, V. C., Purushothaman, A., Stewart, M. D., Thompson, C. A., Vlodavsky, I., Au, J. L., & Sanderson, R. D.
Affiliations: University of Alabama at Birmingham (US)
Cancer and Vascular Biology Research Center Rappaport Faculty of Medicine Haifa Israel
Optimum Therapeutics (United States) (US)
Corresponding author: Sanderson, Ralph D.
ORCID: Ramani, Vishnu C.
Purushothaman, Anurag
Stewart, Mark D.
Au, Jessie L‐S.
Sanderson, Ralph D.
Venue: The FEBS Journal
Publisher: Wiley
Published: 2013-03-04
Volume: 280
Issue: 10
Pages: 2294-2306
ISSN: 1742-464X (ISSN-L)
1742-4658
DOI: 10.1111/febs.12168
PMC: PMC3651779
OpenAlex: W2104368170
Cited by: 189
References: 115
Citations by year: 2026: 7 · 2025: 2 · 2024: 5 · 2023: 9 · 2022: 16 · 2021: 17 · 2020: 18 · 2019: 8 · 2018: 12 · 2017: 11 · 2016: 30 · 2015: 21 · 2014: 24 · 2013: 9
FWCI: 3.22
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: FEBS Journal (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (CA135075, CA138340, R01CA138340, CA138535, R01CA135075, R01CA138535)
National Institute of General Medical Sciences (T32GM008111)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: heparanase, syndecan-1, heparan sulfate proteoglycans, cancer, growth factor signaling, tumor growth, metastasis, angiogenesis, osteolysis, heparanase inhibitors
MeSH terms: Heparanase, Animals, Antineoplastic Agents, Cell Nucleus, Enzyme Activation, Enzyme Inhibitors, Glucuronidase, Heparitin Sulfate, Heparan Sulfate, Humans, Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Hepatocyte Growth Factor, Biomimetic Materials, Syndecan-1, Exosomes

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The heparanase/syndecan‐1 axis in cancer: mechanisms and therapies

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