Transcription factor nuclear factor κB (NFκB) 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. NFκB 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-1β induces nuclear translocation of NFκB 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-1β-treated human umbilical vein endothelial cells can be inhibited by anti-NFκB reagents such as N-acetyl l-cysteine, aspirin, or pentoxifylline. These observations indicate the involvement of NFκB in cancer metastasis and the feasibility of using anti-NFκB reagents in preventing metastasis.
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Ministry of Health and Human Welfare in Japan, and Japanese Foundation for Multidisciplinary Treatment of Cancer.