Identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated haptoglobin in hepatoma cells

Biochem Biophys Res Commun. 2008 Dec 19;377(3):792-6. doi: 10.1016/j.bbrc.2008.10.061. Epub 2008 Oct 23.

Abstract

Fucosylation is one of the most important oligosaccharide modifications and is involved in cancer and inflammation. Recently, fucosylated haptoglobin was identified as a possible tumor marker for pancreatic cancer. The molecular mechanism underlying increases in fucosylated haptoglobin in sera of patients with pancreatic cancer seems to be complicated. Our previous study [N. Okuyama, Y. Ide, M. Nakano, T. Nakagawa, K. Yamanaka, K. Moriwaki, K. Murata, H. Ohigashi, S. Yokoyama, H. Eguchi, O. Ishikawa, T. Ito, M. Kato, A. Kasahara, S. Kawano, J. Gu, N. Taniguchi, E. Miyoshi, Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation, Int. J. Cancer 118 (11) (2006) 2803-2808] demonstrated that pancreatic cancer cells secrete a factor, which induces the production of haptoglobin in hepatoma cells. In the present study, we found that interleukin 6 (IL6) expressed in pancreatic cancer is a factor that induces the haptoglobin production, using a neutralizing antibody for IL6. Real-time PCR analyses revealed the up-regulation of fucosylation regulatory genes after IL6 treatment, resulting increases in fucosylated haptoglobin being revealed by a lectin ELISA. This pathway could be one of the possible mechanisms underlying increases in haptoglobin in sera of patients with pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Culture Media, Conditioned / pharmacology
  • Fucose / metabolism*
  • Fucosyltransferases / genetics
  • Gene Expression
  • Haptoglobins / antagonists & inhibitors
  • Haptoglobins / biosynthesis*
  • Haptoglobins / metabolism
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Liver Neoplasms / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Protein Processing, Post-Translational / genetics

Substances

  • Antibodies
  • Culture Media, Conditioned
  • HP protein, human
  • Haptoglobins
  • Interleukin-6
  • Fucose
  • Fucosyltransferases