Department of Chemistry, University of Oslo , Oslo , Norway.
Front Immunol. 2014 Jul 21;5:325. doi: 10.3389/fimmu.2014.00325. eCollection 2014.
Gangliosides are sialic-acid-containing glycosphingolipids expressed on all vertebrate cells. They are primarily positioned in the plasma membrane with the ceramide part anchored in the membrane and the glycan part exposed on the surface of the cell. These lipids have highly diverse structures, not the least with respect to their carbohydrate chains, with N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc) being the two most common sialic-acid residues in mammalian cells. Generally, human healthy tissue is deficient in NeuGc, but this molecule is expressed in tumors and in human fetal tissues, and was hence classified as an onco-fetal antigen. Gangliosides perform important functions through carbohydrate-specific interactions with proteins, for example, as receptors in cell-cell recognition, which can be exploited by viruses and other pathogens, and also by regulating signaling proteins, such as the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR), through lateral interaction in the membrane. Through both mechanisms, tumor-associated gangliosides may affect malignant progression, which makes them attractive targets for cancer immunotherapies. In this review, we describe how proteins recognize gangliosides, focusing on the molecular recognition of gangliosides associated with cancer immunotherapy, and discuss the importance of these molecules in cancer research.
神经节苷脂是一种含有唾液酸的糖脂，存在于所有脊椎动物细胞表面。它们主要位于质膜中，其神经酰胺部分锚定于膜中，而糖链部分暴露于细胞表面。这些脂质具有高度多样化的结构，尤其是在其碳水化合物链方面，其中 N-乙酰神经氨酸（NeuAc）和 N-羟乙酰神经氨酸（NeuGc）是哺乳动物细胞中最常见的两种唾液酸残基。一般来说，健康的人类组织中缺乏 NeuGc，但这种分子在肿瘤和人类胎儿组织中表达，因此被归类为癌-胚胎抗原。神经节苷脂通过与蛋白质的碳水化合物特异性相互作用发挥重要功能，例如作为细胞间识别的受体，这可被病毒和其他病原体利用，还可通过在膜中的侧向相互作用来调节信号转导蛋白，如表皮生长因子受体（EGFR）和血管内皮生长因子受体（VEGFR）。通过这两种机制，肿瘤相关的神经节苷脂可能会影响恶性进展，这使得它们成为癌症免疫治疗的有吸引力的靶标。在这篇综述中，我们描述了蛋白质如何识别神经节苷脂，重点介绍了与癌症免疫治疗相关的神经节苷脂的分子识别，并讨论了这些分子在癌症研究中的重要性。
