Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA
Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA
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DOI：
10.1093/glycob/cwj042
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发表时间：
2006-02-01
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：
Tabarés, G;Radcliffe, CM;de Llorens, R
前列腺特异性抗原(PSA)是目前用于前列腺癌(PCa)的肿瘤标志物，但其特异性不足以区分前列腺癌和良性前列腺增生症(BPH)。在肿瘤中，糖链的处理通常受到干扰，因此我们调查了PSA糖基化的变化是否可以作为有用的诊断指标。先前我们发现前列腺癌细胞系LNCaP分泌的PSA的糖基化水平与精浆中PSA的糖基化水平有显著差异(正常对照)。因此，我们对来自PCa患者血清的PSA进行了详细的糖链分析，重要的是，确定了Pca血清PSA的糖基化与来自LNCaP细胞系的PSA显著不同。与精浆PSA相比，PCa患者血清中PSA的岩藻糖含量显著降低，2，3-连接唾液酸的含量也减少。通过凝集素检测、糖基化免疫吸附试验和双向电泳，进一步确定了来自PCa患者血清、精浆和LNCaP细胞的PSA糖基化的差异。我们还调查了肿瘤引发的糖基化变化是否反映在血清糖化水平上。通过比较前列腺癌患者血清总糖蛋白和正常血清总糖蛋白释放的糖链，我们发现唾液酸化Lewis x结构比例增加。需要对前列腺癌和前列腺增生症患者血清中PSA的糖基化进行进一步分析，以确定这些糖链差异在区分良性和恶性前列腺状态方面的作用。
Prostate-specific antigen (PSA), the tumor marker currently used for prostate cancer (PCa), is not specific enough to distinguish between PCa and benign prostate hyperplasia (BPH). Glycan processing is normally perturbed in tumors, therefore we investigated whether changes in glycosylation of PSA could be useful diagnostic indicators. Previously we determined that the glycosylation of PSA secreted by the tumor prostate cell line LNCaP differs significantly from that of PSA from seminal plasma (normal control). We therefore undertook a detailed glycan analysis of PSA derived from sera from PCa patients and, importantly, established that the glycosylation of the PCa serum PSA was significantly different from the PSA from the LNCaP cell line. In comparison with seminal plasma PSA, the fucose content of PSA from the PCa patient serum was significantly lower and there was a decrease in a2,3-linked sialic acid. Differences in the glycosylation of PSA derived from PCa patients' sera, seminal plasma, and LNCaP cells were further established by lectin detection, glycosylation immunosorbent assay, and two-dimensional electrophoresis. We also investigated whether the impact of glycosylation changes initiated by the tumor was reflected in the serum glycome. By comparing the glycans released from the total glycoproteins in PCa patient serum with those of normal serum we found an increase in the proportion of sialyl-Lewis x structures. Further analysis of the glycosylation of PSA from PCa and BPH sera will be required in order to determine the utility of these glycan differences to discriminate specifically between benign and malignant prostate states.