EFFECTS OF ANTINUCLEAR 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 suc h as E-selectin, intercellular adhesion molecule 1, and vascular adhes ion molecule 1. These cell adhesion molecules are known to play import ant roles in a critical step of tumor metastasis, arrest of tumor cell s onto the venous or capillary bed of the target organ. NF kappa B is activated by extracellular signals such as those elicited by proinflam matory cytokines, tumor necrosis factor and interleukin 1 (IL-1). sere we demonstrate that IL-1 beta induces nuclear translocation of NF kap pa B in human umbilical vein endothelial cells, followed by induction of cell surface expression of E-selectin, intercellular adhesion molec ule-1, and vascular adhesion molecule 1, and subsequently augments adh esion of those cancer cells expressing sialyl Lewis X antigen, a ligan d 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 involvemen t of NF kappa B in cancer metastasis and the feasibility of using anti -NF kappa B reagents in preventing metastasis.