文章：

癌症的酸甜：聚糖作为新的治疗靶点

The sweet and sour of cancer: glycans as novel therapeutic targets

原文发布日期：2005-07-01

DOI: 10.1038/nrc1649

类型: Review Article

开放获取: 否

要点：

1. Tumours aberrantly express various glycans. Glycans regulate many different aspects of tumour progression, including proliferation, invasion, angiogenesis and metastasis.
2. The proliferation of tumour cells is potentiated by the ability of glycoproteins and glycosphingolipids to directly activate growth-factor receptor tyrosine kinases and by the ability of proteoglycans to function as co-receptors for soluble tumour growth factors.
3. The overexpression of specific glycosyltransferases by tumour cells promotes the formation of tumour glycans that facilitate invasion.
4. Carcinomas commonly overexpress O-linked glycans in the form of cell-surface and secreted mucins that present ligands for adhesion receptors, such as the selectins, which promote the ability of tumour cells to interact with host platelets, leukocytes and endothelial cells. These interactions facilitate haematogenous metastasis of tumour cells.
5. Glycosphingolipids, in the form of gangliosides, are overexpressed by a range of tumours, and their shedding into the bloodstream might impair host immunity to some tumours.
6. During tumour proliferation and invasion, heparan-sulphate proteoglycans (HSPGs) that are present on the surface of tumour cells function as co-receptors to stabilize growth-factor receptor signalling complexes. Secreted HSPGs that are present in the extracellular matrix store growth factors that can be mobilized by the action of tumour heparanases. A similar mechanism that involves endothelial-associated HSPGs and endothelial growth factors facilitates vascular sprouting during tumour angiogenesis.
7. Some glycans can be measured in the bloodstream, and their use as markers of disease burden can be used to screen for specific cancers as well as track response to therapy.
8. Experiments in which glycan function is genetically altered in cell-culture systems or mouse tumour models validate their potential as targets for anticancer therapy.
9. A few glycan-based targeting strategies are currently being tested in clinical trials. As we learn more about the roles of glycans in tumour progression, new targets will continue to emerge for drug design.

要点翻译：

1. 肿瘤异常表达多种聚糖。聚糖调节肿瘤进展的许多不同方面，包括增殖、侵袭、血管生成和转移。
2. 肿瘤细胞的增殖能力通过糖蛋白和糖鞘脂直接激活生长因子受体酪氨酸激酶的能力以及蛋白聚糖作为可溶性肿瘤生长因子共受体的功能而得到增强。
3. 肿瘤细胞过度表达特异性糖基转移酶，促进了有助于侵袭的肿瘤聚糖的形成。
4. 癌通常以细胞表面和分泌型黏蛋白的形式过度表达O-连接聚糖，这些黏蛋白为选择素等粘附受体提供配体，从而增强肿瘤细胞与宿主血小板、白细胞和内皮细胞相互作用的能力。这些相互作用促进了肿瘤细胞的血行转移。
5. 一系列肿瘤会过度表达以神经节苷脂形式存在的糖鞘脂，其脱落进入血流可能会损害宿主对某些肿瘤的免疫力。
6. 在肿瘤增殖和侵袭过程中，肿瘤细胞表面的硫酸乙酰肝素蛋白聚糖（HSPG）作为共受体发挥作用，以稳定生长因子受体信号复合物。细胞外基质中存在的分泌型HSPG储存生长因子，这些生长因子可通过肿瘤乙酰肝素酶的作用被动员。涉及内皮相关HSPG和内皮生长因子的类似机制促进了肿瘤血管生成过程中的血管出芽。
7. 一些聚糖可以在血流中测量，它们作为疾病负荷标志物的用途可用于筛查特定癌症以及追踪治疗反应。
8. 在细胞培养系统或小鼠肿瘤模型中通过基因改变聚糖功能的实验验证了它们作为抗癌治疗靶点的潜力。
9. 目前有一些基于聚糖的靶向策略正在临床试验中进行测试。随着我们对聚糖在肿瘤进展中作用的深入了解，新的药物设计靶点将不断涌现。

英文摘要：

A growing body of evidence supports crucial roles for glycans at various pathophysiological steps of tumour progression. Glycans regulate tumour proliferation, invasion, haematogenous metastasis and angiogenesis, and increased understanding of these roles sets the stage for developing pharmaceutical agents that target these molecules. Such novel agents might be used alone or in combination with operative and/or chemoradiation strategies for treating cancer.

摘要翻译： 

越来越多的证据表明，聚糖在肿瘤进展的多种病理生理步骤中发挥关键作用。聚糖调控肿瘤增殖、侵袭、血行转移和血管生成，对这些作用的深入理解为开发靶向聚糖的药物奠定了基础。这些新型药物可单独使用，也可与手术和/或放化疗策略联合用于癌症治疗。

原文链接：

The sweet and sour of cancer: glycans as novel therapeutic targets