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Heparanase expression upregulates platelet adhesion activity and thrombogenicity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Beijing Inst Transfus Med, Dept Tissue Engn, Beijing, Peoples R China..
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Nova SE Univ, Cell Therapy Inst, Ft Lauderdale, FL 33314 USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 26, 39486-39496 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 7, no 26, 39486-39496 p.
Keyword [en]
heparanase, heparan sulfate, platelet, platelet adhesion, thrombosis
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-299870DOI: 10.18632/oncotarget.8960ISI: 000378614700041OAI: oai:DiVA.org:uu-299870DiVA: diva2:950235
Funder
Swedish Heart Lung FoundationSwedish Research CouncilSwedish Cancer Society
Available from: 2016-07-28 Created: 2016-07-28 Last updated: 2016-07-28Bibliographically approved

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Zhang, Xiao-QunLi, Jin-Ping
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