Leukotriene D4-induced adhesion of Caco-2 cells is mediated by prostaglandin E2 and upregulation of alpha2beta1-integrin.
Cell-cell and extracellular matrix adhesions play important roles in the progression of cancer. We investigated the involvement of the inflammatory mediator leukotriene D4 (LTD4) in the regulation of cell-matrix adhesion of colon cancer (Caco-2) cells. We observed that LTD4 acted via its CysLT1 receptor in these cells to induce increased adhesion to collagen I. LTD4 also enhanced the activation and expression of alpha2beta1-integrins on the cell surface, which we found to be responsible for mediating the increased adhesion to collagen I. LTD4 simultaneously augmented expression of the prostaglandin-generating enzyme cyclooxygenase-2 (COX-2) and increased prostaglandin E2 (PGE2) production in Caco-2 cells. The adhesive capacity of the Caco-2 cells was reduced by specific inhibition of COX-2 and was subsequently restored by PGE2, but not by LTD4. A selective PGE2 receptor antagonist abolished the increased adhesion and the augmented alpha2beta1-integrin expression induced by both PGE2 and LTD4. Summarizing, the inflammatory mediator LTD4 regulates the adhesive properties and migration of the Caco-2 cell line by upregulating COX-2 and stimulating PGE2-induced expression of alpha2beta1-integrins. This suggests that inflammatory mediators such as LTD4 can be involved in the dissemination and survival of colon cancer cells.
D018938:Caco-2 Cells; D002277:Carcinoma / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003092:Colitis / Q000150:complications / Q000276:immunology / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D017998:Leukotriene D4 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology; D014966:Xanthenes / Q000494:pharmacology; D044004:Xanthones
D024042:Collagen Type I; D038982:Integrin alpha2beta1; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D018077:Receptors, Leukotriene; D013449:Sulfonamides; D014966:Xanthenes; D044004:Xanthones; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D017998:Leukotriene D4; C412375:cysteinyl leukotriene receptor 2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C083169:leukotriene D4 receptor