Alkylphospholipids reversibly open epithelial tight junctions.

Autor: Leroy A; Laboratory of Experimental Cancerology, Ghent University Hospital, De Pintelaan, 185, B-9000 Ghent, Belgium., de Bruyne GK, Oomen LC, Mareel MM
Jazyk: angličtina
Zdroj: Anticancer research [Anticancer Res] 2003 Jan-Feb; Vol. 23 (1A), pp. 27-32.
Abstrakt: 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.
Databáze: MEDLINE