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Fucosylated haptoglobin is a novel marker for pancreatic cancer: Detailed analyses of oligosaccharide structures

Journal

PROTEOMICS
Volume 8, Issue 16, Pages 3257-3262

Publisher

WILEY
DOI: 10.1002/pmic.200800046

Keywords

fucosylation; glycomics; haptoglobin; pancreatic cancer; tumor marker

Funding

  1. Dr. Naoyuki Taniguchi Department of Disease Glycomics (Seikagaku Corporation)
  2. Research Institute for Microbial Diseases
  3. Osaka University
  4. Japan Science and Technology Agency (JST)
  5. New Energy and Industrial Technology

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Changes in oligosaccharide structures have been reported in certain types of malignant transformation and thus can be used as tumor markers in certain types of cancer. In the case of pancreatic cancer (PC) cell lines, a variety of fucosylated proteins are secreted into the conditioned media. To identify fucosylated proteins in the sera of patients with PC, we performed Western blot analysis using Aleuria Aurantia Lectin (AAL), which is specific for fucosylated structures. An approximately 40 kD protein was found to be highly fucosylated in PC and 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 colorectal cancer, the incidence was significantly higher in the case of PC. Fucosylated haptoglobin was observed more frequently at the advanced stage of PC and disappeared after operation. Haptoglobin has four sites of N-glycans and site-directed oligosaccharide analysis invoving MS was performed. Site-specific increases in fucosylation of bi-antennary glycans of sites 2 and 4, and of tri-antennary glycans of all sites were observed in PC, compared to in normal volunteers and chronic pancreatitis. Therefore, increases in fucosylation seem to be not due to inflarnation, but cancer itself Coculturing of a human hepatoma cell line, Hep3B, with PC cells-induced production of fucosylated haptoglobin, suggesting that PC produces a factor that induces the production of fucosylated haptoglobin. On clinical investigation of 100 cases of colorectal cancer, cases in which it was located near the liver showed a higher positive rate of filcosylated haptoglobin, suggesting that the location of the cancer might also be an important factor for fucosylated haptoglobin if cancer tissues produce such inducible factors. Thus, fficosylated haptoglobin could become a novel tumor marker for PC and complicated mechanisms would be involved in its production.

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