Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
J Intern Med. 2016 Jul;280(1):97-113. doi: 10.1111/joim.12465. Epub 2016 Jan 8.
Cells are covered by a surface layer of glycans that is referred to as the 'glycocalyx'. In this review, we focus on the role of the glycocalyx in vascular diseases (atherosclerosis, stroke, hypertension, kidney disease and sepsis) and cancer. The glycocalyx and its principal glycosaminoglycans [heparan sulphate (HS) and hyaluronic acid (HA)] and core proteins (syndecans and glypicans) are degraded in vascular diseases, leading to a breakdown of the vascular permeability barrier, enhanced access of leucocytes to the arterial intima that propagate inflammation and alteration of endothelial mechanotransduction mechanisms that protect against disease. By contrast, the glycocalyx on cancer cells is generally robust, promoting integrin clustering and growth factor signalling, and mechanotransduction of interstitial flow shear stress that is elevated in tumours to upregulate matrix metalloproteinase release which enhances cell motility and metastasis. HS and HA are consistently elevated on cancer cells and are associated with tumour growth and metastasis. Later, we will review the agents that might be used to enhance or protect the glycocalyx to combat vascular disease, as well as a different set of compounds that can degrade the cancer cell glycocalyx to suppress cell growth and metastasis. It is clear that what is beneficial for either vascular disease or cancer will not be so for the other. The overarching conclusions are that (i) the importance of the glycocalyx in human medicine is only beginning to be recognized, and (ii) more detailed studies of glycocalyx involvement in vascular diseases and cancer will lead to novel treatment modalities.
细胞表面覆盖着一层糖链，称为“糖萼”。在这篇综述中，我们重点关注糖萼及其主要糖胺聚糖[硫酸乙酰肝素 (HS) 和透明质酸 (HA)]和核心蛋白（连接蛋白和聚糖蛋白）在血管疾病（动脉粥样硬化、中风、高血压、肾病和败血症）和癌症中的作用。糖萼及其主要糖胺聚糖[硫酸乙酰肝素 (HS) 和透明质酸 (HA)]和核心蛋白（连接蛋白和聚糖蛋白）在血管疾病中被降解，导致血管通透性屏障的破坏，白细胞更容易进入动脉内膜，引发炎症，并改变内皮细胞的机械转导机制，从而预防疾病。相比之下，癌细胞上的糖萼通常较为坚固，促进整合素聚集和生长因子信号转导，以及间质流切应力的机械转导，间质流切应力在肿瘤中升高，上调基质金属蛋白酶的释放，增强细胞迁移和转移。HS 和 HA 通常在癌细胞上升高，并与肿瘤生长和转移有关。接下来，我们将回顾可能用于增强或保护糖萼以对抗血管疾病的药物，以及一组不同的化合物，可以降解癌细胞糖萼以抑制细胞生长和转移。很明显，对血管疾病有益的药物不一定对癌症有益，对癌症有益的药物也不一定对血管疾病有益。总而言之：(i) 糖萼在人类医学中的重要性才刚刚开始被认识，(ii) 对糖萼在血管疾病和癌症中的作用的更详细研究将导致新的治疗方法。
