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肝素酶(heparanase)是一种能降低细胞表面硫酸乙酰肝素蛋白聚糖(heparan sulfate proteoglycans,HSPG)的内切糖苷酶。它参与细胞表面细胞外基质(extracellular matrix,ECM)的降解和重塑,促进多配体蛋白聚糖-1(syndecan-1)的合成和释放;它在内涵体和溶酶体等细胞器中具有管家基因的功能,广泛表达于人类的肿瘤细胞中,在侵袭型的动物肿瘤细胞中也过度表达,因此它的过度表达被认为能促进肿瘤的浸润与转移。最近的研究显示,肝素酶能释放硫酸乙酰肝素依赖的生长因子并能产生大量有活性的硫酸乙酰肝素片段,破坏、降解细胞外基底膜屏障,促进肿瘤细胞扩散和转移,并加快血管生成,对肿瘤患者的预后造成了不利的影响。现在,越来越多的肝素酶抑制剂(PI-88、肝素、肽类、硫酸昆布多糖、RNA干扰和苏拉明等)正在被开发出来,并显示出良好的前景。深入研究肝素酶在肿瘤转移和调节中的作用可能会带来肿瘤治疗的新手段。
Heparanase is an endoglycosidase that reduces the cell surface heparan sulfate proteoglycans (HSPG). It participates in the degradation and remodeling of the extracellular matrix (ECM) on the cell surface and promotes the synthesis and release of the syndecan-1. It has the functions of endosomes and organelles such as lysosomes The function of housekeeping genes, widely expressed in human tumor cells, is overexpressed in invasive animal tumor cells, and therefore its overexpression is believed to promote tumor invasion and metastasis. Recent studies have shown that heparanase can release heparan sulfate-dependent growth factor and produce a large number of active heparan sulfate fragments, destroy, degrade extracellular basement membrane barrier, promote tumor cell proliferation and metastasis and accelerate angiogenesis, The prognosis of cancer patients caused adverse effects. Now, more and more heparanase inhibitors (PI-88, heparin, peptides, laminarin sulfate, RNA interference and suramin, etc.) are being developed and show good prospects. In-depth study of the role of heparanase in tumor metastasis and regulation may bring new means of cancer treatment.