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

R. E.B. Seftor*, E. A. Seftor, W. J. Grimes, L. A. Liotta, W. G. Stetler-Stevenson, D. R. Welch, M. J.C. Hendrix

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalMelanoma Research
Volume1
Issue number1
DOIs
StatePublished - Apr 1991

Keywords

  • Cell surface oligosaccharides
  • Glycoprotein processing inhibitors
  • Melanoma
  • Tumour cell invasion

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research

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