Fucosylated haptoglobin is a novel marker for pancreatic cancer: A detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation
Fucosylated haptoglobin is a novel marker for pancreatic cancer: A detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation
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DOI：
10.1002/ijc.21728
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发表时间：
2006-06-01
影响因子：
6.4
通讯作者：
Miyoshi, E
中科院分区：
文献类型：
--
作者：
Okuyama, N;Ide, Y;Miyoshi, E
在某些类型的恶性转化中已经报道了寡糖结构的变化，因此可以用于某些类型癌症的肿瘤标志物。在胰腺癌细胞系的情况下，多种岩藻糖基化蛋白分泌到其条件培养基中。为了鉴定胰腺癌患者血清中的岩藻糖基化蛋白，我们使用岩藻凝集素（AAL）进行蛋白质印迹分析，该凝集素对岩藻糖基化结构具有特异性。在胰腺癌中发现一个类似于40 kD的蛋白质高度岩藻糖基化，N-末端分析显示它是结合珠蛋白的P链。虽然岩藻糖基化触珠蛋白的出现在其他疾病如肝细胞癌、肝硬化、胃癌和结肠癌中已有报道，但在胰腺癌的情况下，其发生率显著更高。岩藻糖基化结合珠蛋白在胰腺癌晚期更常见，手术后消失。从胰腺癌患者血清和胰腺癌细胞系PSN-1的培养基中纯化的触珠蛋白的质谱分析显示，触珠蛋白的α 1-3/α 1-4/α 1-6岩藻糖基化在胰腺癌中增加。当肝癌细胞系Hep 3B与胰腺癌细胞的条件培养基一起培养时，触珠蛋白分泌显著增加。这些发现表明岩藻糖基化结合珠蛋白可以作为胰腺癌的新标记物。结合珠蛋白的岩藻糖基化考虑了两种可能性。一种是胰腺癌细胞本身产生岩藻糖基化结合珠蛋白;另一种是胰腺癌产生一种因子，该因子诱导肝脏中岩藻糖基化结合珠蛋白的产生。(c)2005 Wiley-Liss，Inc.
Changes in oligosaccharide structures have been reported in certain types of malignant transformations and, thus, could be used for tumor markers in certain types of cancer. In the case of pancreatic cancer cell lines, a variety of fucosylated proteins are secreted into their conditioned media. To identify fucosylated proteins in the serum of patients with pancreatic cancer, we performed western blot analyses using Aleuria Aurantica Lectin (AAL), which is specific for fucosylated structures. An similar to 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the P chain of haptoglobin. While the appearance of fucosylated haptoglobin has been reported in other diseases such as hepatocellular carcinoma, liver cirrhosis, gastric cancer and colon cancer, the incidence was significantly higher in the case of pancreatic cancer. Fucosylated haptoglobin was observed more frequently at the advanced stage of pancreatic cancer and disappeared after an operation. A mass spectrometry analysis of haptoglobin purified from the serum of patients with pancreatic cancer and the medium from a pancreatic cancer cell line, PSN-1, showed that the alpha 1-3/alpha 1-4/alpha 1-6 fucosylation of haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B, was cultured with the conditioned media From pancreatic cancer cells, haptoglobin secretion was dramatically increased. These findings suggest that fucosylated haptoglobin could serve as a novel marker for pancreatic cancer. Two possibilities were considered in terms of the fucosylation of haptoglobin. One is that pancreatic cancer cells, themselves, produce fucosylated haptoglobin; the other is that pancreatic cancer produces a factor, which induces the production of fucosylated haptoglobin in the liver. (c) 2005 Wiley-Liss, Inc.