Effect of sialyl Lewis X-glycoliposomes on the inhibition of E-selectin-mediated tumour cell adhesion in vitro

Biochim Biophys Acta. 2004 Jan 28;1660(1-2):31-40. doi: 10.1016/j.bbamem.2003.10.014.

Abstract

The aim of this study was to evaluate the potential of different types of sialyl Lewis X-conjugated liposomes as competitive inhibitors for tumour cell adhesion to endothelial E-selectin. Sterically stabilised liposomes with the sLeX ligand at the terminal end of the polyethyleneglycol (PEG) chain, as well as vesicles that had the ligand embedded within the PEG-layer, were compared to ligand-bearing liposomes without sterical stabilisation. First, 14 different tumour cell lines were characterised for their expression of sialyl Lewis X and/or A. Tumour cell adhesion was characterised in three static assays in vitro using: (i) immobilised E-selectin, (ii) CHO cells, transfected to express E-selectin and (iii) human umbilical vein endothelial cells (HUVEC). Sterically stabilised liposomes with the ligand at the terminal end of the polyethylene chain were the most effective inhibitors in all three assays and inhibited the adhesion of HT29 colon- and Lewis lung (LL) carcinoma cells by about 60-80%. The binding was not affected by a PEG-coating of the liposomes. Sterical stabilisation, on the other hand, completely prevented macrophage uptake (J774 cell line) independently of the presence of the ligand, while plain liposomes were taken up in an amount of 5.4 nmol liposomal lipids/10(6) macrophages.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arylsulfonates
  • CHO Cells
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cells, Cultured
  • Cricetinae
  • E-Selectin / biosynthesis
  • E-Selectin / genetics
  • E-Selectin / physiology*
  • Fluorescent Dyes
  • Glycolipids / chemistry
  • Humans
  • Lewis Blood Group Antigens
  • Ligands
  • Liposomes / chemistry
  • Liposomes / pharmacology*
  • Macrophages / metabolism
  • Oligosaccharides / chemistry*
  • Polyethylene Glycols / chemistry
  • Sialyl Lewis X Antigen
  • Transfection

Substances

  • Arylsulfonates
  • E-Selectin
  • Fluorescent Dyes
  • Glycolipids
  • Lewis Blood Group Antigens
  • Ligands
  • Liposomes
  • Oligosaccharides
  • Sialyl Lewis X Antigen
  • Polyethylene Glycols
  • pyranine