Enhancement in the adhesion of tumor cells to endothelial cells by decreased cholesterol synthesis.
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 B16 melanoma cells prelabeled with 14C-amino acid 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 adhesion. On the other hand, perturbations of the glycosylation in the endothelial cells were without any effect on cell adhesion. The presence of cholesterol dispersion in the growth medium partially reversed the enhancement in cell adhesion caused by the cholesterol inhibitors. Growth in the presence of retinol or dexamethasone (1 microM) also caused enhancement in the adhesiveness of the tumor cells to endothelial cells, possibly because of their effects on cholesterol synthesis. Procaine, a local anesthetic which is known to increase membrane fluidity, also increased the tumor cell-endothelial interaction, suggesting that the membrane fluidity plays an important role in the regulation of cell adhesion.
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Ramachandran
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Sanders
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Melnykovych
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D002784:Cholesterol / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004727:Endothelium / Q000166:cytology*; D006888:Hydroxycholesterols / Q000494:pharmacology; D007653:Ketocholesterols / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives*; D008545:Melanoma / Q000473:pathology*; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000502:physiology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009281:Naphthalenes / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology
D000924:Anticholesteremic Agents; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008563:Membrane Lipids; D009281:Naphthalenes; D012176:Retinoids; C012258:mevastatin; C007997:25-hydroxycholesterol; D003907:Dexamethasone; D002784:Cholesterol; D008148:Lovastatin; C003001:7-ketocholesterol