糖鞘脂分析技术及相关疾病研究进展

Advances in Analysis of Glycosphingolipids and Related Diseases

糖鞘脂是一类广泛分布在动物细胞膜表面的糖脂类物质,它在调控细胞识别、黏附、增殖以及凋亡等方面均有重要的生物学作用.本综述主要讨论了在现代分析技术范畴中,糖鞘脂的鉴定及其糖链结构的分离与解析方面的研究进展和糖鞘脂在癌症等疾病发生发展中所起的生物学功能,以及糖鞘脂作为疾病治疗靶标的可能性.随着现代仪器技术,尤其是质谱技术和色谱-质谱联用技术的发展,糖鞘脂的分离与检测也进入了高速发展的时代.目前,使用质谱技术在肝癌、结直肠癌、乳腺癌等恶性肿瘤的组织样本中均发现了不同种类糖鞘脂不同程度的异常表达.其中,岩藻糖基化的糖鞘脂上调表达在众多癌症糖鞘脂检测中尤为突出,故岩藻糖基化的糖鞘脂可能会成为一类癌症的早期诊断标志物.近年来,随着对糖鞘脂理解的不断深入,糖鞘脂在诸多疾病,如癌症血管生成过程中的功能研究成为了热点之一.例如,从肿瘤细胞表面脱落的大多数糖鞘脂在肿瘤微环境中主要起到了促进血管生成的作用,而与此相反的是,另一种结构简单的神经节苷脂GM3却起到了抑制血管生成的作用.本综述汇集了对上述现象在分子水平上的不同解读以及利用此现象对癌症靶向治疗的研究与探索,并对基于抑制糖鞘脂合成的靶向治疗的发展前景进行了分析展望.

Glycosphingolipids are ubiquitous cell membrane and act significantly in many bioprocesses such as cell adhesion, embryonic development, signal transduction and carcinogenesis. The advances of structural analysis of glycosphingolipids using modern analytical instruments, the separation and identification of glycosphingolipids, as well as the biological functions of glycosphingolipids in the progress of diseases were thoroughly discussed in this review. The analysis of glycosphingolipid has made spectacular progress due to the rapid development of modem analytical technology, especially mass spectrometry and the tandem application of chromatography-mass spectrometry. Presently, the use of mass spectrometry in discovering aberrant levels of multiple glycosphingolipids in various malignancies has indicated that the fucosylated glycosphingolipids elevated in the tumor tissues of hepatocellular carcinoma, colorectal cancer, breast cancer and so on. This phenomenon made fucosylated glycosphingolipid a potentially novel cancer marker for early diagnosis. Furthermore, phenotypic and functional research on glycosphingolipids is becoming a popular aspect of glycolipid study, particularly in the relevancy between glycosphingolipids and angiogenesis. For instance, glycosphingolipids shed from the surface of tumor cells act positively on angiogenesis, nevertheless, GM3, a simple ganglioside, acts reversely as a proangiogenesic factor in the tumor microenvironment. This review summarized several cellular hypothesis of the phenomenon above, illustrated the explorations in glycosphingolipid-targeted therapy against malignancies to provide further visions on glycosphingolipid research.