Glycosylation status of haptoglobin in sera of patients with prostate cancer vs. benign prostate disease or normal subjects
Glycosylation status of haptoglobin in sera of patients with prostate cancer vs. benign prostate disease or normal subjects
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DOI：
10.1002/ijc.22958
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发表时间：
2008-01-01
影响因子：
6.4
通讯作者：
Hakomori, Sen-Itiroh
中科院分区：
文献类型：
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作者：
Fujimura, Tsutomu;Shinohara, Yasuro;Hakomori, Sen-Itiroh
我们研究了前列腺癌患者血清中结合珠蛋白的化学水平和糖基化状态，并与良性前列腺疾病和正常受试者进行了比较，结果如下。(i)前列腺癌患者血清中结合珠蛋白水平明显升高。(ii)唾液酸化的双触角聚糖是所有3种来源的结合珠蛋白中的主要结构，而不考虑N-连接聚糖的不同位点。N184处的N-连接聚糖仅为双触角，并且在前列腺癌与良性前列腺疾病之间没有差异。(iii)三触角N-连接岩藻糖基化聚糖，携带至少1个唾液酸-路易斯（x/a）触角，主要位于前列腺癌P链氨基酸203-215序列内的N207或N211上，在良性前列腺疾病中极少。在正常受试者中未观察到岩藻糖基化聚糖。在前列腺癌中β链的N241处观察到一个较小的三触角N-连接聚糖，而在良性前列腺疾病中不存在。(iv)尽管前列腺癌触珠蛋白与单克隆抗体RM 2具有交叉反应性，但这些N-连接结构均未显示出预期存在的具有GaINAc β 4（NeuAc α 3）GaI β 3（NeuAc α 6）GlcNAc β Gal或其类似物的二唾液酸化触角。(v)首次在前列腺癌触珠蛋白中鉴定出少量的O-糖基化。在还原性β-消除后，通过甲基化和质谱分析鉴定单唾液酸和二唾液酸核心1型O-连接结构。没有发现与该O-聚糖核心连接的特异性RM 2或其他肿瘤相关糖基表位存在的证据。总之，结合珠蛋白的水平在前列腺癌患者的血清中增强，并且附着于其β链的限定肽区域的N-聚糖的特征在于增强的分支以及天线岩藻糖基化。(C)2007 Wiley-Liss，Inc.
We studied chemical level and glycosylation status of haptoglobin in sera of patients with prostate cancer, as compared to benign prostate disease and normal subjects, with the following results. (i) Haptoglobin level was enhanced significantly in sera of prostate cancer. (ii) Sialylated bi-antennary glycans were the dominant structures in haptoglobins from all 3 sources, regardless of different site of N-linked glycan. The N-linked glycans at N184 were exclusively bi-antennary, and showed no difference between prostate cancer vs. benign prostate disease. (iii) Tri-antennary N-linked, fucosylated glycans, carrying at least 1 sialyl-Lewis(x/a) antenna, were predominantly located on N207 or N211 within the amino acid 203-215 sequence of the P-chain of prostate cancer, and were minimal in benign prostate disease. Fucosylated glycans were not observed in normal subjects. A minor tri-antennary N-linked glycan was observed at N241 of the beta-chain in prostate cancer, which was absent in benign prostate disease. (iv) None of these N-linked structures showed the expected presence of disialylated antennae with GaINAc beta 4(NeuAc alpha 3)GaI beta 3(NeuAc alpha 6)GlcNAc beta Gal, or its analogue, despite cross-reactivity of prostate cancer haptoglobin with monoclonal antibody RM2. (v) Minor levels of O-glycosylation were identified in prostate cancer haptoglobin for the first time. Mono-and disialyl core Type 1 O-linked structures were identified after reductive beta-elimination followed by methylation and mass spectrometric analysis. No evidence was found for the presence of specific RM2 or other tumor-associated glycosyl epitopes linked to this O-glycan core. In summary, levels of haptoglobin are enhanced in sera of prostate cancer patients, and the N-glycans attached to a defined peptide region of its beta-chain are characterized by enhanced branching as well as antenna fucosylation. (C) 2007 Wiley-Liss, Inc.