Heparanase expression upregulates platelet adhesion activity and thrombogenicity.
Oncotarget
; 7(26): 39486-39496, 2016 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-27129145
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adesividade Plaquetária
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Regulação da Expressão Gênica
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Glucuronidase
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article