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.
© 2013 The Authors Journal compilation © 2013 FEBS.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Biomimetic Materials / pharmacology
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Cell Nucleus / enzymology
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Cell Nucleus / pathology
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Exosomes / metabolism
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Exosomes / pathology
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Gene Expression Regulation, Neoplastic*
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Glucuronidase / antagonists & inhibitors
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Glucuronidase / metabolism*
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Heparitin Sulfate / metabolism
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Hepatocyte Growth Factor / metabolism
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Humans
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Neoplasms / drug therapy*
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Neoplasms / enzymology
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Neoplasms / pathology
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Signal Transduction
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Syndecan-1 / genetics
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Syndecan-1 / metabolism*
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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HGF protein, human
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SDC1 protein, human
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Syndecan-1
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Hepatocyte Growth Factor
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Heparitin Sulfate
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heparanase
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Glucuronidase