Glycosylation of serum ribonuclease 1 indicates a major endothelial origin and reveals an increase in core fucosylation in pancreatic cancer
Glycosylation of serum ribonuclease 1 indicates a major endothelial origin and reveals an increase in core fucosylation in pancreatic cancer
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DOI：
10.1093/glycob/cwm002
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发表时间：
2007-04-01
期刊：
影响因子：
4.3
通讯作者：
Peracaula, Rosa
中科院分区：
文献类型：
--
作者：
Barrabes, Silvia;Pages-Pons, Lluis;Peracaula, Rosa
人胰腺核糖核酸酶1(RNase1)是一种主要由胰腺表达的糖蛋白，也存在于内皮细胞中。胰腺癌(PAC)的诊断仍然很困难，因此需要寻找敏感和特异的标记物。以往的研究表明，来自健康人胰腺的RNase1只含有中性糖链，而来自PAC细胞的RNase1含有唾液酸化的结构。为了确定这些与糖肿瘤细胞相关的改变是否也是血清RNase1的特征并可作为PAC的标志，我们对血清RNase1的糖基化进行了分析，并探讨了血清RNase1的来源。对2例PAC患者和2例正常对照的血清RNase1进行纯化，并用高效液相色谱(HPLC)测序和质谱法分析其糖链。尽管正常和肿瘤血清RNase1含有相同的糖链结构，但PAC血清RNase1中主要唾液酸化的双天线糖链的核心岩藻糖基化增加了40%。这一比例的变化可能预示着RNase1的一个肿瘤相关糖型亚群，这可能为PAC提供一个生物标志物。对几种内皮细胞系EA.hy926、人脐静脉内皮细胞(HUVEC)、人乳腺微血管内皮细胞(HuMMEC)和人肺微血管内皮细胞(HuLEC)的RNase1进行了双向电泳，结果表明，EA.hy926的RNase1与血清RNase1的糖基化图谱非常相似，提示内皮细胞是该酶的主要来源。
Human pancreatic ribonuclease 1 (RNase 1) is a glycoprotein expressed mainly by the pancreas and also found in endothelial cells. The diagnosis of pancreatic cancer (PaC) remains difficult and therefore the search for sensitive and specific markers is required.Previous studies showed that RNase 1 from human healthy pancreas contained only neutral glycans, whereas RNase 1 from PaC cell lines contained sialylated structures. To determine whether these glycan tumor cell-associated changes were also characteristic of serum RNase 1 and could be used as a marker of PaC, we have analyzed the glycosylation of serum RNase 1. The origin of serum RNase 1 was also investigated. Serum RNase 1 from two PaC patients and two controls was purified and the glycans analyzed by high-performance liquid chromatography (HPLC)-based sequencing and mass spectrometry. Although normal and tumor serum RNase 1 contained the same glycan structures, there was an increase of 40% in core fucosylation in the main sialylated biantennary glycans in the PaC serum RNase 1. This change in proportion would be indicative of a subset of tumor-associated glycoforms of RNase 1, which may provide a biomarker for PaC. Two-dimensional electrophoresis of the RNase 1 from several endothelial cell lines, EA.hy926, human umbilical vein endothelial cells (HUVEC), human mammary microvessel endothelial cells (HuMMEC), and human lung microvessel endothelial cells (HuLEC), showed basically the same pattern and was also very similar to that of serum RNase 1. RNase 1 from EA.hy926 was then purified and presented a glycosylation profile very similar to that from serum RNase 1, suggesting that endothelial cells are the main source of this enzyme.