Heparanase mediates cell adhesion independent of its enzymatic activity
Heparanase mediates cell adhesion independent of its enzymatic activity
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DOI：
10.1096/fj.02-0773com
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发表时间：
2003-06-01
期刊：
影响因子：
4.8
通讯作者：
Vlodavsky, I
中科院分区：
文献类型：
--
作者：
Goldschmidt, O;Zcharia, E;Vlodavsky, I
乙酰肝素酶是一种内切β-D-葡萄糖醛酸酶，其裂解硫酸乙酰肝素，并参与多种生理和病理过程。在这项研究中，我们报告了一种新的直接参与细胞粘附的乙酰肝素酶。我们证明，乙酰肝素酶在非粘附性淋巴瘤细胞中的表达诱导细胞粘附的早期阶段，只要该酶在细胞表面上表达。乙酰肝素酶介导的细胞与细胞外基质（ECM）的粘附导致整合素依赖的细胞铺展、桩蛋白的酪氨酸磷酸化和肌动蛋白细胞骨架的重组。这种表面结合的酶还通过重建的基底膜增强细胞侵袭。细胞粘附增强细胞表面乙酰肝素酶，无论细胞转染活性或点突变失活酶，表明乙酰肝素酶作为一种粘附分子的功能，独立于其糖苷内切酶活性。乙酰肝素酶作为ECM降解酶和细胞粘附分子的组合特征强调了其在涉及细胞粘附、迁移和侵袭的过程中的重要性，包括胚胎发育、新生血管形成和癌症转移。
Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate and is implicated in diverse physiological and pathological processes. In this study we report on a novel direct involvement of heparanase in cell adhesion. We demonstrate that expression of heparanase in nonadherent lymphoma cells induces early stages of cell adhesion, provided that the enzyme is expressed on the cell surface. Heparanase-mediated cell adhesion to extracellular matrix (ECM) results in integrin-dependent cell spreading, tyrosine phosphorylation of paxillin, and reorganization of the actin cytoskeleton. The surface-bound enzyme also augments cell invasion through a reconstituted basement membrane. Cell adhesion was augmented by cell surface heparanase regardless of whether the cells were transfected with active or point mutated inactive enzyme, indicating that heparanase functions as an adhesion molecule independent of its endoglycosidase activity. The combined feature of heparanase as an ECM-degrading enzyme and a cell adhesion molecule emphasizes its significance in processes involving cell adhesion, migration, and invasion, including embryonic development, neovascularization, and cancer metastasis.