Heparanase expression upregulates platelet adhesion activity and thrombogenicity
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Hao Cui1,*, Ying-xia Tan1,2,*, Cecilia Österholm3,4, Xiao Zhang5, Ulf Hedin3, Israel Vlodavsky6 and Jin-Ping Li1
1 Department of Medical Biochemistry and Microbiology, SciLifeLab Uppsala, The Biomedical Center, University of Uppsala, Husargatan, Uppsala, Sweden
2 Department of Tissue Engineering, Beijing Institute of Transfusion Medicine, Beijing, China
3 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
4 Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL, USA
5 Department of Neuroscience and Pharmacology, University of Uppsala, Husargatan, Uppsala, Sweden
6 Cancer and Vascular Biology Research Center Rappaport, Faculty of Medicine, Technion, Haifa, Israel
* These authors have contributed equally to this work
Jin-Ping Li, email:
Keywords: heparanase, heparan sulfate, platelet, platelet adhesion, thrombosis
Received: April 01, 2016 Accepted: April 06, 2016 Published: April 25, 2016
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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