Effects of anti-nuclear factor kappa B reagents in blocking adhesion of human cancer cells to vascular endothelial cells.
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.
Tozawa
K
K
Department of Molecular Genetics, Nagoya City University Medical School, Japan.
Sakurada
S
S
Kohri
K
K
Okamoto
T
T
D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009362:Neoplasm Metastasis; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1