Gold compounds inhibit adhesion of human cancer cells to vascular endothelial cells

Transcription factor NF-κB controls the expression of a number of genes including those for cell adhesion molecules such as E-selectin, ICAM-1 and VCAM-1. These cell adhesion molecules are known to play important roles in a critical step of tumor metastasis; the arrest of tumor cells on the venous or capillary bed of the target organ. NF-κB is activated by extracellular signals such as those elicited by the proinflammatory cytokines, TNF and IL-1. Here we demonstrate that IL-1β induces nuclear translocation of NF-κB in human umbilical vein endothelial cells (HUVEC) followed by induction of cell surface expression of E-selectin, ICAM-1 and VCAM-1, and subsequently augments adhesion of cancer cells expressing sialyl Lewis antigen, a ligand of E-selectin. We also demonstrated that the adhesion of tumor cells to IL-1β-treated HUVEC was inhibited by gold compounds such as aurothioglucose and aurothiomalate. These observations indicate the involvement of NF-κB in cancer metastasis and suggest the feasibility of using gold compounds to prevent metastasis.