The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum
The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer patient's serum
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DOI：
10.1093/glycob/cwn022
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发表时间：
2008-06-01
期刊：
影响因子：
4.3
通讯作者：
Rudd, Pauline M.
中科院分区：
文献类型：
--
作者：
Storr, Sarah J.;Royle, Louise;Rudd, Pauline M.
MUC1 是一种高分子量糖蛋白，在乳腺癌中过度表达。癌症中 MUC1 的异常 O 联糖基化与疾病进展有关。我们研究了从晚期乳腺癌患者血清中纯化的 MUC1 的 O-连接糖基化。通过肼解释放 O-聚糖，并通过液相色谱-电喷雾电离-质谱法和高效液相色谱结合连续外切糖苷酶消化进行分析。核心 1 型聚糖 (83%) 占主导地位，这也证实了高水平的唾液酸化：80% 的聚糖是单唾液酸化、二唾液酸化或三唾液酸化。核心 2 型结构贡献了约 17% 的指定聚糖，癌胎儿 Thomsen-Friedenreich (TF) 抗原 (Gal beta 1-3GalNAc) 占总聚糖的 14%。有趣的是，鉴定出两个核心 1 型聚糖，其唾液酸 α 2-8 连接到唾液酸化的核心 1 型结构（占总聚糖库的 9%）。这是首次对乳腺癌患者血清中的 MUC1 进行 O 聚糖分析；结果表明，在常用来表达重组 MUC1 的细胞系中，T47D 细胞系加工的聚糖与患者来源的材料最相似。
MUC1 is a high molecular weight glycoprotein that is overexpressed in breast cancer. Aberrant O-linked glycosylation of MUC1 in cancer has been implicated in disease progression. We investigated the O-linked glycosylation of MUC1 purified from the serum of an advanced breast cancer patient. O-Glycans were released by hydrazinolysis and analyzed by liquid chromatography-electrospray ionization-mass spectrometry and by high performance liquid chromatography coupled with sequential exoglycosidase digestions. Core 1 type glycans (83%) dominated the profile which also confirmed high levels of sialylation: 80% of the glycans were mono-, di- or trisialylated. Core 2 type structures contributed approximately 17% of the assigned glycans and the oncofoetal Thomsen-Friedenreich (TF) antigen (Gal beta 1-3GalNAc) accounted for 14% of the total glycans. Interestingly, two core 1 type glycans were identified that had sialic acid alpha 2-8 linked to sialylated core 1 type structures (9% of the total glycan pool). This is the first O-glycan analysis of MUC1 from the serum of a breast cancer patient; the results suggest that amongst the cell lines commonly used to express recombinant MUC1 the T47D cell line processes glycans that are most similar to patient-derived material.