Alkylphospholipids reversibly open epithelial tight junctions

Anticancer Res. Jan-Feb 2003;23(1A):27-32.

Abstract

Alkylphospholipids, such as the antitumor ether lipid 1-O-octadecyl-2-O-methylglycero-3-phosphocholine, modulate cancer cell invasion through changes in the adherens junction E-cadherin complex, a major organizer of epithelia. We wanted to know whether alkylphospholipids would also change tight junctions, molecular complexes that seal cell-to-cell contacts in polarised epithelia. Therefore, human colorectal cancer cell layers T84 were established in two-compartment culture chambers and the functional integrity of tight junctions was evaluated through their transepithelial electrical resistance. Incorporation of alkylphospholipids causes a rapid and reversible decrease of transepithelial electrical resistance. This decrease is due to an increased paracellular permeability and is temperature-independent. Unlike methyl-beta-cyclodextrin, alkyl-phospholipids do not specifically displace lipids from raft-like membrane domains. Nevertheless, alkylphospholipids change the detergent-solubility of zonula occludens-protein and occludin. Our data, together with the literature, indicate that non-toxic doses of alkylphospholipids affect more than one cell-cell adhesion complex, probably through their incorporation into the plasma membrane lipid bilayer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cholesterol / metabolism
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology
  • Cyclodextrins / pharmacology
  • Detergents / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Mannitol / pharmacokinetics
  • Microscopy, Confocal
  • Phospholipid Ethers / pharmacology*
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacology
  • Precipitin Tests
  • Tight Junctions / drug effects*
  • Tritium
  • Tumor Cells, Cultured
  • beta-Cyclodextrins*

Substances

  • Antineoplastic Agents
  • Cyclodextrins
  • Detergents
  • Phospholipid Ethers
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • Tritium
  • Phosphorylcholine
  • edelfosine
  • perifosine
  • Mannitol
  • miltefosine
  • Cholesterol