糖链受体在肿瘤微环境中的功能机制研究

顾建新+阮元元

摘 要：糖链是继蛋白质、核酸之后的第三条生命之链。研究表明，正常细胞表面超过70%的蛋白被糖基化修饰。在肿瘤中，糖基化的改变及糖链异常是一种非常普遍的现象，糖链异常在肿瘤增殖、迁移、侵袭、免疫逃避和耐药等过程中起重要作用。因此阐明糖链结构及其受体在肿瘤发生发展过程中的作用，有助于在此基础上寻找肿瘤的治疗靶点以及进行基于糖类的创新药物研究，这是当今国际上生命科学研究中最受关注的领域之一。肿瘤是一个严重的公共卫生问题，开辟肿瘤诊断和治疗的新理念和新策略是一项十分迫切的国家需求。该项目旨在通过糖化学与糖生物学两大学科的交叉和整合，以我国发病率较高的肺癌、肝癌、乳腺癌和宫颈癌为主要研究对象，从糖科学的新视角探索糖链在肿瘤发生、发展和转移过程中的功能及分子机制；采用糖化学生物学方法，拟解决两个关键科学问题：①肿瘤功能相关糖链探针的可获得性问题；②肿瘤相关糖链的变化规律和功能机制。该项目主要研究内容将紧紧围绕当前糖化学生物学发展中的若干重要前沿问题，从肿瘤细胞和肿瘤微环境两个方向，从糖链结构特征、糖链合成调控和糖链功能实现等方面入手，运用糖链探针研究肿瘤相关特征性糖链结构、其调控机制及其功能性凝集素受体，揭示糖链在肿瘤发生、发展和转移中的生物学功能和分子机制，发现肿瘤中糖链相关的诊断和治疗靶点。另一方面，以解决糖链的高效合成为导向，采用化学及酶法两条互补的途径合成肿瘤相关的糖链及其缀合物分子，并以此为探针来验证特异性糖链在肿瘤生物学功能中的作用；进一步设计合成糖链及其模拟物，对肿瘤的糖链异常进行干预和调控，发展新的肿瘤治疗手段。

关键词：糖化学 糖生物学 肿瘤 糖链探针 糖基转移酶 凝集素

Abstract：Sugar chain is the third chain of life ，following protein and nucleic acid.Studies show that more than 70% of the normal cell surface proteinsare modified with glycosylation. In tumors， abnormal changes of glycosylation and sugar chain are common phenomenons.Abnormity of sugar chain plays an important role in tumor proliferation， migration， invasion， immune escape and chemoresistance.As a result ， clarifying sugar chain structure and the function of its receptors in the development of tumors will contribute to find tumor therapeutic targets and do innovative drug research.This is one of the most popular areas of scientific research nowadays. Tumor is a serious public health problem. Opening up new ideas of the tumor diagnosis and treatment is a very pressing needs for a country.With the crossover and integration of chemical and biological sugar，this project aims to explore the function and molecular mechanism of the sugar chain in the process of tumorigenesis， development and metastasis， on the basis of higher incidence of lung cancer， liver cancer， breast cancer and cervical cancer in our country as the main research object. Sugar chemical biology method is used to solve two key scientific problems：① The availability of sugar chain probe about tumor function；②The changes of the sugar chain and functional mechanism related to tumor. The main research of this project will closely involve the current important frontier issues in the development of chemical biology， from both tumor cells and tumor microenvironment aspects.We will also use sugar chain probe to explore tumor related sugar chain structure， its regulatory mechanism and functional lectin receptors， evealing the sugar chain in the occurrence， development and metastasis of tumor biology function and molecular mechanism of tumours in the sugar chain related diagnostic and therapeutic targets. On the other hand， in order to solve the efficiency of the synthesis of sugar chain， two complementary ways of using chemical and enzymatic synthesis will be used to synthesize the tumor associated sugar chain and its conjugated molecules.In this way，we can find a probe to verify the special role of sugar chain in tumor biology and further design synthetic sugar chain and its simulation.This will contribute to the intervention of tumor related abnormal regulation of sugar chain and develop new tumor treatment.

Key Words：Glycochemistry； Glycobiology； Tumor； Glycan probe； Glycosyltransferase； Lectin

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