title: Heparanase expression upregulates platelet adhesion activity and thrombogenicity.
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.
authors.affiliation: Department of Medical Biochemistry and Microbiology, SciLifeLab Uppsala, The Biomedical Center, University of Uppsala, Husargatan, Uppsala, Sweden.
authors.forename: Hao
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Medical Biochemistry and Microbiology, SciLifeLab Uppsala, The Biomedical Center, University of Uppsala, Husargatan, Uppsala, Sweden.|Department of Tissue Engineering, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Tan
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Österholm
authors.affiliation: Department of Neuroscience and Pharmacology, University of Uppsala, Husargatan, Uppsala, Sweden.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hedin
authors.affiliation: Cancer and Vascular Biology Research Center Rappaport, Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.affiliation: Department of Medical Biochemistry and Microbiology, SciLifeLab Uppsala, The Biomedical Center, University of Uppsala, Husargatan, Uppsala, Sweden.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Li
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D002469:Cell Separation; D002712:Chlorides / Q000737:chemistry; D003433:Crosses, Genetic; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000737:chemistry; D006497:Heparan Sulfate; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D051149:Selenoprotein P / Q000378:metabolism; D013927:Thrombosis; D015854:Up-Regulation; D000099175:Heparanase
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D005966:Glucuronidase; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D019007:P-Selectin; D051149:Selenoprotein P; D000099175:Heparanase; C546937:SELP protein, human; C024555:ferric chloride
keywords: heparan sulfate; heparanase; platelet; platelet adhesion; thrombosis