Gold compounds inhibit adhesion of human cancer cells to vascular endothelial cells.
Transcription factor NF-kappaB 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-kappaB is activated by extracellular signals such as those elicited by the proinflammatory cytokines, TNF and IL-1. Here we demonstrate that IL-1beta induces nuclear translocation of NF-kappaB 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-1beta-treated HUVEC was inhibited by gold compounds such as aurothioglucose and aurothiomalate. These observations indicate the involvement of NF-kappaB in cancer metastasis and suggest the feasibility of using gold compounds to prevent metastasis.
Tozawa
Keiichi
K
Department of Urology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan.
Kawai
Noriyasu
N
Hayashi
Yutaro
Y
Sasaki
Shoichi
S
Kohri
Kenjiro
K
Okamoto
Takashi
T
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D017612:Gold Compounds / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D017612:Gold Compounds; D007375:Interleukin-1; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1