uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Heparanase neutralizes the anticoagulation properties of heparin and low-molecular-weight heparin
Show others and affiliations
2006 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 4, no 3, 560-565 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Heparanase is a mammalian endo-D-glucuronidase that cleaves heparan sulfate (HS) in the extracellular matrix and cell surface. It is preferentially expressed by cells of the immune system and tumor cells. Heparanase overexpression in experimental tumor models results in increased angiogenesis and metastasis. Heparin and low-molecular weight heparin (LMWH) inhibit HS degradation by heparanase. OBJECTIVE: To investigate whether heparanase cleaves heparin and LMWH, and elucidate its effect on blood coagulation. METHODS: Heparin and LMWH were incubated with recombinant heparanase and subjected to measurements of molecular size (size exclusion chromatography) and anticoagulant activity (plasma APTT-activated thromboplastin time, and anti-Xa activity). APTT was also measured in plasma samples of transgenic mice overexpressing heparanase, in comparison with control mice. RESULTS: Incubation of heparin and LMWH with heparanase resulted in degradation of these substrates, as revealed by a significant decrease in their molecular weight. This was correlated with a marked suppression of the anticoagulant activity of heparin and LMWH, as indicated by a decreased effect on APTT and anti-Xa activity, respectively, when human plasma was added. Transgenic mice overexpressing heparanase exhibited a significantly shorter APTT than control mice. CONCLUSION: Heparanase is capable of degrading heparin and LMWH, so that its overexpression by tumor cells may contribute to heparin resistance, commonly occurring in cancer patients. In view of the complexity of the currently available heparanase activity assays, we propose an indirect approach to quantify heparanase activity by measuring the decrease in plasma APTT or anti-Xa activity exerted by the enzyme under the defined conditions.

Place, publisher, year, edition, pages
2006. Vol. 4, no 3, 560-565 p.
Keyword [en]
Cancer progression, coagulation, heparanase, heparin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-22549DOI: 10.1111/j.1538-7836.2006.01792.xISI: 000235168900018PubMedID: 16460439OAI: oai:DiVA.org:uu-22549DiVA: diva2:50322
Available from: 2007-01-18 Created: 2007-01-18 Last updated: 2017-12-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=16460439&dopt=Citation

Authority records BETA

Li, Jin-Ping

Search in DiVA

By author/editor
Li, Jin-Ping
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Journal of Thrombosis and Haemostasis
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 634 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf