title: Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation.
abstract: 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 approximately 40 kD protein was found to be highly fucosylated in pancreatic cancer and an N-terminal analysis revealed that it was the beta 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.
authors.affiliation: Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Okuyama
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ide
authors.forename: Miyako
authors.initials: M
authors.lastname: Nakano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Kanako
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Kenta
authors.initials: K
authors.lastname: Moriwaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohigashi
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ito
authors.forename: Michio
authors.initials: M
authors.lastname: Kato
authors.forename: Akinori
authors.initials: A
authors.lastname: Kasahara
authors.forename: Sunao
authors.initials: S
authors.lastname: Kawano
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D005260:Female; D005914:Globins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D009844:Oligosaccharides; C067666:hepatoglobin; D005914:Globins