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Heparanase expression upregulates platelet adhesion activity and thrombogenicity
Heparanase is an endo-glucuronidase that specifically cleaves heparan sulfate (HS) and heparin polysaccharides. The enzyme is expressed at low levels in normal tissues, but is often upregulated under pathological conditions such as cancer and inflammation. Normal human platelets express exceptionall...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129947/ https://www.ncbi.nlm.nih.gov/pubmed/27129145 http://dx.doi.org/10.18632/oncotarget.8960 |
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author | Cui, Hao Tan, Ying-xia Österholm, Cecilia Zhang, Xiao Hedin, Ulf Vlodavsky, Israel Li, Jin-Ping |
author_facet | Cui, Hao Tan, Ying-xia Österholm, Cecilia Zhang, Xiao Hedin, Ulf Vlodavsky, Israel Li, Jin-Ping |
author_sort | Cui, Hao |
collection | PubMed |
description | Heparanase is an endo-glucuronidase that specifically cleaves heparan sulfate (HS) and heparin polysaccharides. The enzyme is expressed at low levels in normal tissues, but is often upregulated under pathological conditions such as cancer and inflammation. Normal human platelets express exceptionally high levels of heparanase, but the functional consequences of this feature remain unknown. We investigated functional roles of heparanase by comparing the properties of platelets expressing high (Hpa-tg) or low (Ctr) levels of heparanase. Upon activation, Hpa-tg platelets exhibited a much stronger adhesion activity as compared to Ctr platelets, likely contributing to a higher thrombotic activity in a carotid thrombosis model. Furthermore, we found concomitant upregulated expression of both heparanase and CD62P (P-selectin) upon activation of mouse and human platelets. As platelets play important roles in tumor metastasis, these findings indicate contribution of the platelet heparanase to hyper-thrombotic conditions often seen in patients with metastatic cancer. |
format | Online Article Text |
id | pubmed-5129947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51299472016-12-11 Heparanase expression upregulates platelet adhesion activity and thrombogenicity Cui, Hao Tan, Ying-xia Österholm, Cecilia Zhang, Xiao Hedin, Ulf Vlodavsky, Israel Li, Jin-Ping Oncotarget Research Paper Heparanase is an endo-glucuronidase that specifically cleaves heparan sulfate (HS) and heparin polysaccharides. The enzyme is expressed at low levels in normal tissues, but is often upregulated under pathological conditions such as cancer and inflammation. Normal human platelets express exceptionally high levels of heparanase, but the functional consequences of this feature remain unknown. We investigated functional roles of heparanase by comparing the properties of platelets expressing high (Hpa-tg) or low (Ctr) levels of heparanase. Upon activation, Hpa-tg platelets exhibited a much stronger adhesion activity as compared to Ctr platelets, likely contributing to a higher thrombotic activity in a carotid thrombosis model. Furthermore, we found concomitant upregulated expression of both heparanase and CD62P (P-selectin) upon activation of mouse and human platelets. As platelets play important roles in tumor metastasis, these findings indicate contribution of the platelet heparanase to hyper-thrombotic conditions often seen in patients with metastatic cancer. Impact Journals LLC 2016-04-23 /pmc/articles/PMC5129947/ /pubmed/27129145 http://dx.doi.org/10.18632/oncotarget.8960 Text en Copyright: © 2016 Cui et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Cui, Hao Tan, Ying-xia Österholm, Cecilia Zhang, Xiao Hedin, Ulf Vlodavsky, Israel Li, Jin-Ping Heparanase expression upregulates platelet adhesion activity and thrombogenicity |
title | Heparanase expression upregulates platelet adhesion activity and thrombogenicity |
title_full | Heparanase expression upregulates platelet adhesion activity and thrombogenicity |
title_fullStr | Heparanase expression upregulates platelet adhesion activity and thrombogenicity |
title_full_unstemmed | Heparanase expression upregulates platelet adhesion activity and thrombogenicity |
title_short | Heparanase expression upregulates platelet adhesion activity and thrombogenicity |
title_sort | heparanase expression upregulates platelet adhesion activity and thrombogenicity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129947/ https://www.ncbi.nlm.nih.gov/pubmed/27129145 http://dx.doi.org/10.18632/oncotarget.8960 |
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