フコシル化ハプトグロビンは新規膵臓がんマーカーである FUCOSYLATED HAPTOGLOBIN IS A NOVEL MARKER FOR PANCREATIC CANCER: A DETAILED ANALYSIS ON THE OLIGOSACCHARIDE STRUCTURE AND A POSSIBLE MECHANISM FOR FUCOSYLATION

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Author(s)

    • 奥山 紀子 Okuyama Noriko
    • 大阪大学大学院医学系研究科生化学|大阪大学大学院医学系研究科分子生物学 Department of Biochemistry,Osaka University Graduate School of Medicine|Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine
    • 中川 勉 Nakagawa Tsutomu
    • 大阪大学大学院医学系研究科生化学 Department of Biochemistry,Osaka University Graduate School of Medicine
    • 村田 幸平 Murata Kohei
    • 大阪大学大学院医学系研究科外科学 Department of Surgery, Osaka University Graduate School of Medicine
    • 近藤 昭宏 Kondo Akihiro
    • 大阪大学大学院医学系研究科糖鎖治療学 Department of Glycotherapeutics, Osaka University Graduate School of Medicine
    • 三善 英知 Miyoshi Eiji
    • 大阪大学大学院医学系研究科生化学 Department of Biochemistry,Osaka University Graduate School of Medicine

Abstract

Changes in oligosaccharide structures have been reported in 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 approximately 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the b chain of haptoglobin. While levels of fucosylated haptoglobin have 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 a1-3/a1-4 /a1-6 fucosylation of haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B was cultured with the conditioned media of pancreatic cancer cells, the secretion of haptoglobin 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.

Changes in oligosaccharide structures have been reported in 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 approximately 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the b chain of haptoglobin. While levels of fucosylated haptoglobin have 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 a1-3/a1-4 /a1-6 fucosylation of haptoglobin was increased in pancreatic cancer. When a hepatoma cell line, Hep3B was cultured with the conditioned media of pancreatic cancer cells, the secretion of haptoglobin 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.

Journal

  • Abstracts for Annual Meeting of Japanese Proteomics Society

    Abstracts for Annual Meeting of Japanese Proteomics Society 2005(0), 122-122, 2005

    Japanese Proteomics Society (Japan Human Proteome Organisation)

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