Effects of anti-nuclear factor kappa B reagents in blocking adhesion of human cancer cells to vascular endothelial cells

Cancer Res. 1995 Sep 15;55(18):4162-7.

Abstract

Transcription factor nuclear factor kappa B (NF kappa B) controls gene expression of a number of genes including cell adhesion molecules such as E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 1. These cell adhesion molecules are known to play important roles in a critical step of tumor metastasis, arrest of tumor cells onto the venous or capillary bed of the target organ. NF kappa B is activated by extracellular signals such as those elicited by proinflammatory cytokines, tumor necrosis factor and interleukin 1 (IL-1). Here we demonstrate that IL-1 beta induces nuclear translocation of NF kappa B in human umbilical vein endothelial cells, followed by induction of cell surface expression of E-selectin, intercellular adhesion molecule-1, and vascular adhesion molecule 1, and subsequently augments adhesion of those cancer cells expressing sialyl Lewis X antigen, a ligand to E-selectin. We have also demonstrated that the adhesion of tumor cells to IL-1 beta-treated human umbilical vein endothelial cells can be inhibited by anti-NF kappa B reagents such as N-acetyl L-cysteine, aspirin, or pentoxifylline. These observations indicate the involvement of NF kappa B in cancer metastasis and the feasibility of using anti-NF kappa B reagents in preventing metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Adhesion
  • Cell Adhesion Molecules / biosynthesis
  • Cells, Cultured
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-1 / pharmacology
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / physiology*
  • Neoplasm Metastasis*
  • Reactive Oxygen Species
  • Vascular Cell Adhesion Molecule-1

Substances

  • Cell Adhesion Molecules
  • Interleukin-1
  • NF-kappa B
  • Reactive Oxygen Species
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1