【摘要】：糖鞘脂是一類廣泛分布在動(dòng)物細(xì)胞膜表面的糖脂類物質(zhì),它在調(diào)控細(xì)胞識(shí)別、黏附、增殖以及凋亡等方面均有重要的生物學(xué)作用.本綜述主要討論了在現(xiàn)代分析技術(shù)范疇中,糖鞘脂的鑒定及其糖鏈結(jié)構(gòu)的分離與解析方面的研究進(jìn)展和糖鞘脂在癌癥等疾病發(fā)生發(fā)展中所起的生物學(xué)功能,以及糖鞘脂作為疾病治療靶標(biāo)的可能性.隨著現(xiàn)代儀器技術(shù),尤其是質(zhì)譜技術(shù)和色譜-質(zhì)譜聯(lián)用技術(shù)的發(fā)展,糖鞘脂的分離與檢測也進(jìn)入了高速發(fā)展的時(shí)代.目前,使用質(zhì)譜技術(shù)在肝癌、結(jié)直腸癌、乳腺癌等惡性腫瘤的組織樣本中均發(fā)現(xiàn)了不同種類糖鞘脂不同程度的異常表達(dá).其中,巖藻糖基化的糖鞘脂上調(diào)表達(dá)在眾多癌癥糖鞘脂檢測中尤為突出,故巖藻糖基化的糖鞘脂可能會(huì)成為一類癌癥的早期診斷標(biāo)志物.近年來,隨著對糖鞘脂理解的不斷深入,糖鞘脂在諸多疾病,如癌癥血管生成過程中的功能研究成為了熱點(diǎn)之一.例如,從腫瘤細(xì)胞表面脫落的大多數(shù)糖鞘脂在腫瘤微環(huán)境中主要起到了促進(jìn)血管生成的作用,而與此相反的是,另一種結(jié)構(gòu)簡單的神經(jīng)節(jié)苷脂GM3卻起到了抑制血管生成的作用.本綜述匯集了對上述現(xiàn)象在分子水平上的不同解讀以及利用此現(xiàn)象對癌癥靶向治療的研究與探索,并對基于抑制糖鞘脂合成的靶向治療的發(fā)展前景進(jìn)行了分析展望.
[Abstract]:Saccharin is a kind of glycolipids widely distributed on the surface of animal cell membrane. It plays an important biological role in regulating cell recognition, adhesion, proliferation and apoptosis. In this review, the recent advances in the identification of sphingolipids, the separation and analysis of their sugar chain structures, and their biological functions in the occurrence and development of cancer and other diseases are mainly discussed in the field of modern analytical techniques. And the possibility of saccharin as a target for disease treatment. With the development of modern instrument technology, especially mass spectrometry and chromatography-mass spectrometry, the separation and detection of glycolipid has entered the era of rapid development. At present, mass spectrometry has been used to detect abnormal expression of different kinds of sphingolipid in tissues of liver cancer, colorectal cancer, breast cancer and other malignant tumors. Among them, the up-regulation of sphingolipid by fucosylation is especially prominent in many cancers, so the glycosylated sphingolipid may become an early diagnostic marker for a class of cancer. In recent years, with the deepening of understanding of glycolipid, the functional study of glycolipid in many diseases, such as cancer angiogenesis, has become one of the hot spots. For example, most of the sphingolipids removed from the surface of tumor cells play a major role in promoting angiogenesis in the tumor microenvironment, whereas another simple ganglioside GM3 inhibits angiogenesis. This review brings together different interpretations of the above phenomena at molecular level, as well as the research and exploration of cancer targeted therapy using this phenomenon, and the prospect of targeted therapy based on inhibition of glycolipid biosynthesis is analyzed and prospected.
【作者單位】： 西北大學(xué)生命科學(xué)學(xué)院功能糖組學(xué)實(shí)驗(yàn)室;
【基金】：國家自然科學(xué)基金基地建設(shè)能力提高項(xiàng)目(J1210063)資助~~
【分類號】：Q26;R363

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