Altered glycosylation pattern allows the distinction between prostate-specific antigen (PSA) from normal and tumor origins
Altered glycosylation pattern allows the distinction between prostate-specific antigen (PSA) from normal and tumor origins
复制标题
DOI：
10.1093/glycob/cwg041
复制
发表时间：
2003-06-01
期刊：
影响因子：
4.3
通讯作者：
de Llorens, R
中科院分区：
文献类型：
--
作者：
Peracaula, R;Tabarés, G;de Llorens, R
前列腺特异性抗原（PSA）是前列腺上皮细胞分泌的一种糖蛋白。PSA目前被用作前列腺癌的标志物，因为高水平的PSA指示肿瘤情况。然而，PSA测试仍然缺乏区分良性前列腺增生和前列腺癌的特异性。为了确定PSA糖基化是否可以提供区分来自正常和肿瘤来源的PSA的手段，通过测序分析和质谱法对来自精液和前列腺癌细胞（LNCaP细胞系）的PSA进行N-聚糖表征。来自正常PSA的聚糖（对应于低和高pI PSA组分）为唾液酸化双触角复合物结构，其中一半在低pI PSA组分中被二唾液酸化，而在高pI PSA组分中大部分被单唾液酸化。从LNCaP细胞的PSA纯化到同质，其聚糖分析显示出显着不同的模式，特别是在双触角复合物结构的外端。与唾液酸化的正常PSA聚糖相比，LNCaP PSA寡糖均为中性，并且含有更高的岩藻糖含量。在10 - 15%的结构中，岩藻糖与α 1 - 2半乳糖连接，形成正常PSA中不存在的H2表位。GalNAc在LNCaP聚糖中增加到65%，而在正常PSA中仅存在于25%的结构中。这些碳水化合物的差异允许区分PSA从正常和肿瘤的起源，并建议一个有价值的生化诊断和随访的工具。
Prostate-specific antigen (PSA) is a glycoprotein secreted by prostate epithelial cells. PSA is currently used as a marker of prostate carcinoma because high levels of PSA are indicative of a tumor situation. However, PSA tests still suffer from a lack of specificity to distinguish between benign prostate hyperplasia and prostate cancer. To determine whether PSA glycosylation could provide a means of differentiating between PSA from normal and tumor origins, N-glycan characterization of PSA from seminal fluid and prostate cancer cells (LNCaP cell line) by sequencing analysis and mass spectrometry was carried out. Glycans from normal PSA (that correspond to low and high pI PSA fractions) were sialylated biantennary complex structures, half of them being disialylated in the low pI PSA fraction and mostly monosialylated in the high pI PSA. PSA from LNCaP cells was purified to homogeneity, and its glycan analysis showed a significantly different pattern, especially in the outer ends of the biantennary complex structures. In contrast to normal PSA glycans, which were sialylated, LNCaP PSA oligosaccharides were all neutral and contained a higher fucose content. In 10-15% of the structures fucose was linked alpha1-2 to galactose, forming the H2 epitope absent in normal PSA. GalNAc was increased in LNCaP glycans to 65%, whereas in normal PSA it was only present in 25% of the structures. These carbohydrate differences allow a distinction to be made between PSA from normal and tumor origins and suggest a valuable biochemical tool for diagnosis and follow-up purposes.