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The heparanase/syndecan‐1 axis in cancer: mechanisms and therapies
Open accessAbstract
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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“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].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [182]
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Metadata
- 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.
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2013-03-04
- Volume
- 280
- Issue
- 10
- Pages
- 2294-2306
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- 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
- 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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