Document Detail


Heparanase regulates levels of syndecan-1 in the nucleus.
MedLine Citation:
PMID:  19305494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Syndecan-1 is a transmembrane heparan sulfate-bearing proteoglycan known to regulate multiple biological functions at the cell surface and within the extracellular matrix. Its functional activity can be modulated by heparanase, an enzyme that cleaves heparan sulfate chains and whose expression has been associated with an aggressive phenotype in many cancers. In addition to remodeling syndecan-1 by cleaving its heparan sulfate chains, heparanase influences syndecan-1 location by upregulating expression of enzymes that accelerate its shedding from the cell surface. In the present study we discovered that heparanase also alters the level of nuclear syndecan-1. Upon upregulation of heparanase expression or following addition of recombinant heparanase to myeloma cells, the nuclear localization of syndecan-1 drops dramatically as revealed by confocal microscopy, western blotting and quantification by ELISA. This effect requires enzymatically active heparanase because cells expressing high levels of mutated, enzymatically inactive heparanase, failed to diminish syndecan-1 levels in the nucleus. Although heparan sulfate function within the nucleus is not well understood, there is emerging evidence that it may act to repress transcriptional activity. The resulting changes in gene expression facilitated by the loss of nuclear syndecan-1 could explain how heparanase enhances expression of MMP-9, VEGF, tissue factor and perhaps other effectors that condition the tumor microenvironment to promote an aggressive cancer phenotype.
Authors:
Ligong Chen; Ralph D Sanderson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-23
Journal Detail:
Title:  PloS one     Volume:  4     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2009  
Date Detail:
Created Date:  2009-03-23     Completed Date:  2009-04-24     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e4947     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cell Nucleus / metabolism*
Gene Expression Regulation
Glucuronidase / genetics,  metabolism*
Humans
Recombinant Proteins / genetics,  metabolism
Syndecan-1 / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
CA013148/CA/NCI NIH HHS; CA103054/CA/NCI NIH HHS; CA135075/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Recombinant Proteins; 0/Syndecan-1; EC 3.2.1.-/heparanase; EC 3.2.1.31/Glucuronidase
Comments/Corrections

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