Alkylphospholipids reversibly open epithelial tight junctions.
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.
Leroy
Ancy
A
Laboratory of Experimental Cancerology, Ghent University Hospital, De Pintelaan, 185, B-9000 Ghent, Belgium.
de Bruyne
Georges K P
GK
Oomen
Lauran C J M
LC
Mareel
Marc M
MM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003505:Cyclodextrins / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008353:Mannitol / Q000493:pharmacokinetics; D018613:Microscopy, Confocal; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011233:Precipitin Tests; D019108:Tight Junctions / Q000187:drug effects*; D014316:Tritium; D014407:Tumor Cells, Cultured; D047392:beta-Cyclodextrins
D000970:Antineoplastic Agents; D003505:Cyclodextrins; D003902:Detergents; D010742:Phospholipid Ethers; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D014316:Tritium; D010767:Phosphorylcholine; C026659:edelfosine; C105905:perifosine; D008353:Mannitol; C039128:miltefosine; D002784:Cholesterol