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

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Melanoma invasion is a critical factor in metastasis.
• Cell surface oligosaccharide structure influences cell behavior and invasiveness.
• Golgi alpha-mannosidases play a role in N-linked oligosaccharide processing.

Purpose of the Study:

• To investigate the effect of inhibiting Golgi alpha-mannosidases on human melanoma cell invasion.
• To determine the correlation between altered oligosaccharide composition and melanoma cell invasiveness.
• To examine the impact of these inhibitors on cell adhesion and type IV collagenase expression.

Main Methods:

• Pretreatment of human melanoma cell lines with swainsonine or deoxymannojirimycin.
• In vitro invasion assays using a reconstituted basement membrane.
• Assessment of cell adhesion to basement membrane and endothelial cells.
• Analysis of cell surface oligosaccharide changes via lectin binding.
• Measurement of type IV collagenase mRNA expression.

Main Results:

• Swainsonine and deoxymannojirimycin dose-dependently decreased melanoma cell invasion.
• Inhibitor treatment altered cell surface oligosaccharide structure, affecting lectin binding.
• Cell adhesion to basement membrane and endothelial cells decreased by 25-33%.
• A correlative decrease in type IV collagenase mRNA expression was observed.
• Inhibitory effects on invasion and collagenase expression were reversible.

Conclusions:

• Inhibition of Golgi alpha-mannosidases alters melanoma cell surface oligosaccharides.
• These alterations correlate with decreased cell invasion and reduced type IV collagenase expression.
• Targeting N-linked oligosaccharide processing may represent a therapeutic strategy for melanoma.