文章：

硫酸肝素糖胺聚糖在癌症中的作用

Roles of heparan-sulphate glycosaminoglycans in cancer

原文发布日期：2002-07-01

DOI: 10.1038/nrc842

类型: Review Article

开放获取: 否

要点：

1. Heparan-sulphate glycosaminoglycans (HSGAGs) act at the cell–extracellular-matrix (ECM) interface to modulate cell signalling, thereby regulating how a cell perceives its environment.
2. HSGAGs interact with various extracellular signalling molecules: growth factors, morphogens, enzymes and chemokines. The specificity of these interactions is dependent on HSGAG sequence, spacing of binding sites and the three-dimensional structure of the HSGAG chain.
3. HSGAGs, depending on location and sequence, impinge on tumour onset and progression in various ways, some of which are pro-tumorigenic and others of which are anti-tumorigenic.
4. HSGAGs at the tumour-cell surface actively modulate the tumorigenic process by regulating autocrine signalling loops that lead to unregulated cell growth.
5. HSGAGs impinge on how an organism responds to a growing tumour, including the recruitment of cells of the immune system to the tumour site, formation of a fibrin shell around the tumour that acts as a protective barrier and development of new blood vessels to the site of the growing tumour.
6. Compelling clinical evidence indicates that pharmacological doses of heparin, a highly sulphated HSGAG, can have a marked effect on tumour metastasis. Clinical trials have been designed to determine the exact benefits of heparin therapy in cancer.
7. In addition, the low-molecular-weight heparins (LMWHs) — a series of heparin fragments that share many of heparin's activities, including its anticoagulant effect, but lack several of its side effects — might show even greater antitumour activity.
8. The advent of HSGAG sequencing technologies promises to usher in a new generation of LMWHs with potent antitumour activity.

要点翻译：

1. 硫酸乙酰肝素糖胺聚糖（HSGAGs）在细胞-细胞外基质（ECM）界面发挥作用，通过调节细胞信号传导来调控细胞对周围环境的感知。
2. HSGAGs与多种细胞外信号分子相互作用：生长因子、形态发生素、酶和趋化因子。这些相互作用的特异性取决于HSGAG的序列、结合位点间距及其三维结构。
3. 根据定位和序列的不同，HSGAGs以多种方式影响肿瘤的发生与发展，其中某些作用促进肿瘤发生，而另一些则抑制肿瘤发生。
4. 肿瘤细胞表面的HSGAGs通过调节自分泌信号环路来主动调控肿瘤发生过程，这些环路会导致细胞生长失控。
5. HSGAGs影响机体对生长中肿瘤的反应机制，包括免疫细胞向肿瘤部位的募集、肿瘤周围形成作为保护屏障的纤维蛋白外壳，以及向生长肿瘤部位的新血管生成。
6. 令人信服的临床证据表明，高硫酸化的HSGAG药物——肝素——的药理剂量能显著影响肿瘤转移。目前设计的临床试验旨在确定肝素疗法在癌症治疗中的确切效益。
7. 此外，低分子量肝素（LMWHs）——系列具有肝素多种活性（包括抗凝血作用）但规避了其部分副作用的肝素片段——可能展现出更强的抗肿瘤活性。
8. HSGAG测序技术的出现，有望催生具有强效抗肿瘤活性的新一代低分子量肝素。

英文摘要：

Cell-surface/extracellular-matrix heparan-sulphate glycosaminoglycans (HSGAGs) are complex polysaccharides that are ubiquitous in nature, and that regulate several aspects of cancer biology, including tumorigenesis, tumour progression and metastasis. Recently gained insights into the structure of HSGAGs have extended our understanding of their role in the oncogenic process. At present, clinical trials are examining the anticancer properties of exogenous highly sulphated HSGAGs, including heparin and low-molecular-weight heparins, in addition to small oligosaccharide heparin mimetics. Combined with our more intricate understanding of HSGAG structure, this emerging structure–activity approach opens exciting avenues for the generation of polysaccharide-based anticancer therapeutics.

摘要翻译： 

细胞表面/细胞外基质中的硫酸乙酰肝素糖胺聚糖（HSGAGs）是普遍存在于自然界的复杂多糖，调控肿瘤发生、进展和转移等多个癌症生物学过程。近期对HSGAG结构的深入认识拓展了我们对它们在致癌过程中作用的理解。目前，临床试验正在研究外源性高硫酸化HSGAGs（包括肝素和低分子量肝素）以及小分子寡糖肝素模拟物的抗癌特性。结合我们对HSGAG结构日益精细的认识，这种新兴的结构-活性策略为开发基于多糖的抗癌治疗药物开辟了令人振奋的前景。

原文链接：

Roles of heparan-sulphate glycosaminoglycans in cancer