Mammalian heparanase: what is the message?

Mammalian heparanase: what is the message?
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DOI:
10.1111/j.1582-4934.2007.00039.x
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发表时间:
2007-05
影响因子:
5.3
通讯作者:
David G
David G
中科院分区:
医学2区
文献类型:
--
作者:
Vreys V;David G

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硫酸肝素蛋白聚糖是细胞表面和细胞外基质中普遍存在的大分子。许多细胞外基质蛋白、生长因子、形态因子、细胞因子、趋化因子和凝血因子受到硫酸肝素的结合和调节。硫酸肝素的降解因此可能深刻影响细胞和组织功能。虽然有证据表明可能存在几种硫酸肝素降解内切葡萄糖醛酸酶(肝素酶),但迄今为止只发现了一种编码功能性肝素酶的转录物:肝素酶-1。在这篇综述的第一部分,我们讨论了目前关于硫酸肝素蛋白聚糖的知识和它们的多功能相互作用的功能重要性。第二部分综述了肝素酶-1的分子特性、作用机制、底物特异性、表达模式、细胞活化和定位等方面的研究进展。此外,我们回顾了涉及肝素酶-1在几个正常和病理过程中的数据,重点是肿瘤转移和血管生成,以及该分子潜在的直接信号功能的证据。在这种情况下,我们还简要讨论了肝素酶-2,这是肝素酶-1的一个有趣的近亲同源物,到目前为止,还没有硫酸肝素降解活性可以证明。
Heparan sulphate proteoglycans are ubiquitous macromolecules of cell surfaces and extracellular matrices. Numerous extracellular matrix proteins, growth factors, morphogens, cytokines, chemokines and coagulation factors are bound and regulated by heparan sulphate. Degradation of heparan sulphate thus potentially profoundly affects cell and tissue function. Although there is evidence that several heparan sulphate-degrading endoglucuronidases (heparanases) might exist, so far only one transcript encoding a functional heparanase has been identified: heparanase-1. In the first part of this review, we discuss the current knowledge about heparan sulphate proteoglycans and the functional importance of their versatile interactions. In the second part, we summarize recent findings that have contributed to the characterization of heparanase-1, focusing on the molecular properties, working mechanism, substrate specificity, expression pattern, cellular activation and localization of this enzyme. Additionally, we review data implicating heparanase-1 in several normal and pathological processes, focusing on tumour metastasis and angiogenesis, and on evidence for a potentially direct signalling function of the molecule. In that context, we also briefly discuss heparanase-2, an intriguing close homologue of heparanase-1, for which, so far, no heparan sulphate-degrading activity could be demonstrated.
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