Cui Hao, Tan Ying-Xia, Österholm Cecilia, Zhang Xiao, Hedin Ulf, Vlodavsky Israel, Li Jin-Ping
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.
Oncotarget. 2016 Jun 28;7(26):39486-39496. doi: 10.18632/oncotarget.8960.
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.
乙酰肝素酶是一种内切葡糖醛酸酶，可特异性切割硫酸乙酰肝素（HS）和肝素多糖。该酶在正常组织中低水平表达，但在癌症和炎症等病理条件下常上调。正常人类血小板表达异常高水平的乙酰肝素酶，但其功能后果尚不清楚。我们通过比较表达高水平（Hpa-tg）或低水平（Ctr）乙酰肝素酶的血小板特性，研究了乙酰肝素酶的功能作用。激活后，与Ctr血小板相比，Hpa-tg血小板表现出更强的粘附活性，这可能导致颈动脉血栓形成模型中更高的血栓形成活性。此外，我们发现小鼠和人类血小板激活后，乙酰肝素酶和CD62P（P-选择素）的表达同时上调。由于血小板在肿瘤转移中起重要作用，这些发现表明血小板乙酰肝素酶对转移性癌症患者常见的高血栓形成状态有贡献。
