Document Detail


The heparanase/syndecan-1 axis in cancer: mechanisms and therapies.
MedLine Citation:
PMID:  23374281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Vishnu C Ramani; Anurag Purushothaman; Mark D Stewart; Camilla A Thompson; Israel Vlodavsky; Jessie L-S Au; Ralph D Sanderson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review     Date:  2013-03-04
Journal Detail:
Title:  The FEBS journal     Volume:  280     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-10     Completed Date:  2013-07-02     Revised Date:  2014-05-30    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2294-306     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors Journal compilation © 2013 FEBS.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology
Biomimetic Materials / pharmacology
Cell Nucleus / enzymology,  pathology
Enzyme Activation
Enzyme Inhibitors / pharmacology
Exosomes / metabolism,  pathology
Gene Expression Regulation, Neoplastic*
Glucuronidase / antagonists & inhibitors,  metabolism*
Heparitin Sulfate / metabolism
Hepatocyte Growth Factor / metabolism
Humans
Neoplasms / drug therapy*,  enzymology,  pathology
Signal Transduction
Syndecan-1 / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
CA135075/CA/NCI NIH HHS; CA138340/CA/NCI NIH HHS; CA138535/CA/NCI NIH HHS; R01 CA135075/CA/NCI NIH HHS; R01 CA138340/CA/NCI NIH HHS; R01 CA138535/CA/NCI NIH HHS; T32 GM008111/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/HGF protein, human; 0/SDC1 protein, human; 0/Syndecan-1; 67256-21-7/Hepatocyte Growth Factor; 9050-30-0/Heparitin Sulfate; EC 3.2.1.-/heparanase; EC 3.2.1.31/Glucuronidase
Comments/Corrections

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