Attachment of human colon cancer cells to vascular endothelium is enhanced by N-acetylglucosaminyltransferase V.

Abstract

Expression of N-acetylglucosaminyltransferase V (GnT-V) in colon cancer has been shown to be related to hematogenous metastasis and poor prognosis. To investigate the mechanism by which cancer cells expressing GnT-V metastasize to distant organs, we established GnT-V-overexpressing DLD-1 and WiDr cells (human colon cancer cell lines) by transfecting them with a GnT-V expression vector. Attachment to endothelial cells expressing E-selectin was studied, and expression of the E-selectin ligand, sialyl Lewis x, in colon cancer cells was investigated. Both of the cell lines showed reduced adhesion to fibronectin as compared with mock transfectants. In contrast, attachment to human umbilical vein endothelial cells expressing E-selectin was significantly enhanced by GnT-V expression (p < 0.01). Sialyl Lewis x is a ligand for E-selectin and a marker for poor prognosis of colon cancer. Its synthesis in cells has been shown to involve GnT-V. We demonstrated that expression of sialyl Lewis x in colon cancer cells was induced by GnT-V expression. These results suggest that GnT-V induces sialyl Lewis x expression and leads colon cancer cells to metastasize by enhancing their ability to attach to vascular endothelium in distant organs, such as liver or lung. Inhibition of GnT-V activity may prevent metastasis in colon cancer patients with high sialyl Lewis x expression.

• Authors: Kohei Murata, Eiji Miyoshi, Shinji Ihara, Shingo Noura, Masao Kameyama, Osamu Ishikawa, Yuichiro Doki, Terumasa Yamada, Hiroaki Ohigashi, Yo Sasaki, Masahiko Higashiyama, Takehiko Tarui, Yoshikazu Takada, Reiji Kannagi, Naoyuki Taniguchi, Shingi Imaoka
• Journal: Oncology (Oncology) Vol. 66 Issue 6 Pg. 492-501 ( 2004) ISSN: 0030-2414 [Print] Switzerland
• PMID: 15452379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 S. Karger AG, Basel

Chemical References

• Biomarkers, Tumor
• E-Selectin
• Fibronectins
• Membrane Glycoproteins
• Oligosaccharides
• Receptors, Fibroblast Growth Factor
• Sialoglycoproteins
• Sialyl Lewis X Antigen
• cysteine-rich fibroblast growth factor receptor
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase

Topics

• Biomarkers, Tumor (metabolism)
• Cell Adhesion (drug effects)
• Colonic Neoplasms (metabolism, physiopathology)
• E-Selectin (metabolism)
• Endothelium, Vascular (metabolism, physiopathology)
• Fibronectins (metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Membrane Glycoproteins (metabolism)
• N-Acetylglucosaminyltransferases (metabolism, pharmacology)
• Oligosaccharides (metabolism)
• Prognosis
• Receptors, Fibroblast Growth Factor (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sialoglycoproteins
• Sialyl Lewis X Antigen
• Up-Regulation