Modulation of the adhesion process cell-cell for prostaglandim E2 in cells of human colon adenocarcinoma.
Cyclooxygenase and its derived, prostaglandin E2 (PGE2), have been shown to stimulate the growth of cancer cells and promote migration and invasiveness in colorectal carcinoma cells. Here, we have investigated the effects of PGE2 treatmenton the junctional complex (JC) in an epithelial cell line derived from human colon adenocarcinoma, Caco-2. Cells were treated with PGE2 (1 amp;#956;M) and the effects on thejunctional complex were monitored at different times. Alterations of tight and adherens junction components were observed by measuring the transepithelial electrical resistance (TER), by immunofluorescence and immunoblotting and electronmicroscopy analyses (TEM). Our results showed that cells treated for 15 minutes with PGE2 (1 amp;#956;M) presented a decrease of the TER in about 40%. When cell monolayerswere analyzed by TEM, it was possible to observe wide spaces at the adherens junction region in cells treated for 15, 30 and 60 minutes compared to non-treatedcells, which present well defined JC. In addition, we found that the tight junctions were apparently preserved after all times of treatment with PGE2. However, using theruthenium red technique, we showed that the tight junctions are not functional, as verified by the junction?s permeability to the markes. Alterations in the pattern ofjunctional proteins distribution were observed for E-cadherin, b-catenin, occludin, ZO- 1 and claudin-1, -4, mainly after the first minutes of treatment. Our results shown thatPGE2 caused alterations of the junctional complex, leading to disturbance of the paracellular permeability to ions, disruption of cell-cell contact, redistribution of the main proteins of tight and adherens junctions in Caco-2 cells.
Advisor:Maurilio José Soares; José Andrés Morgado Díaz
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Date of Publication:09/29/2006