Human melanoma cell invasion is inhibited in vitro by swainsonine and deoxymannojirimycin with a concomitant decrease in collagenase IV expression

Abstract

A 48 h pretreatment of two malignant and invasive human melanoma cell lines with either swainsonine (an inhibitor of Golgi alpha-mannosidase II) or deoxymannojirimycin (a Golgi alpha-mannosidase I inhibitor) resulted in a dose-dependent decrease in the cells' ability to invade a reconstituted basement membrane in vitro. This effect was reversible within 48 h of removing the drugs. Treatment with either drug resulted in both cell lines being more resistant to the cytotoxic effects of the lectin leukoagglutinin (PHA-L) and more sensitive to the lectin concanavalin A which indirectly indicated a change in the cell surface oligosaccharide composition and structure consistent with the known effects of these drugs on N-linked oligosaccharide processing. A 25-33% decrease was noted in the adhesion of treated cells to either a reconstituted basement membrane or human umbilical vein endothelial cell monolayer while no change was measured in the cells' proliferative rates. A correlative decrease was observed, however, in the expression of human type IV collagenase mRNA which was recovered within 48 h of removing the drugs. These results suggest that a correlation exists between the drug-induced changes in the cell surface oligosaccharide composition and structure with a concomitant decrease in the mRNA and secreted levels of type IV collagenase and the ability of these cells to invade.