Enhancement in the Adhesion of Tumor Cells to Endothelial Cells by Decreased Cholesterol Synthesis1

Adhesive interactions between tumor cells and the endothelial cells are presumed to be an obligatory step in the metastatic process. Using an in vitro model, we have examined the role of endothelial lipids in the regulation of this interaction. The cholesterol levels of bovine aorta endothelial cell monolayers were inhibited by the addition of compactin, 25-hydroxycholesterol, or 7-ketocholesterol. Metastatic B!6 melanoma cells prelabeled with MC-aminoacid mixture were then deposited on this monolayer as a suspension and, at various time intervals, the number of cells adhering to the monolayer was determined. The results indicated that inhibition of cellular cholesterol caused enhancement in cell adhe sion. On the other hand, perturbations of the glycosylation in the endo thelial cells were without any effect on cell adhesion. The presence of cholesterol dispersion in the growth medium partially reversed the en hancement in cell adhesion caused by the cholesterol inhibitors. Growth in the presence of retinol or dexamethasone (1 MM)also caused enhance ment in the adhesiveness of the tumor cells to endothelial cells, possibly because of their effects on cholesterol synthesis. Procaine, a local anes thetic which is known to increase membrane fluidity, also increased the tumor cell-endothelial interaction, suggesting that the membrane fluidityplays an important role in the regulation of cell adhesion.