Leukotriene D 4-induced adhesion of Caco-2 cells is mediated by prostaglandin E 2 and upregulation of α2β1-integrin

Abstract

Cell-cell and extracellular matrix adhesions play important roles in the progression of cancer. We investigated the involvement of the inflammatory mediator leukotriene D 4 (LTD 4) in the regulation of cell-matrix adhesion of colon cancer (Caco-2) cells. We observed that LTD 4 acted via its CysLT 1 receptor in these cells to induce increased adhesion to collagen I. LTD 4 also enhanced the activation and expression of α2β1-integrins on the cell surface, which we found to be responsible for mediating the increased adhesion to collagen I. LTD 4 simultaneously augmented expression of the prostaglandin-generating enzyme cyclooxygenase-2 (COX-2) and increased prostaglandin E 2 (PGE 2) 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 PGE 2, but not by LTD 4. A selective PGE 2 receptor antagonist abolished the increased adhesion and the augmented α2β1-integrin expression induced by both PGE 2 and LTD 4. Summarizing, the inflammatory mediator LTD 4 regulates the adhesive properties and migration of the Caco-2 cell line by upregulating COX-2 and stimulating PGE 2-induced expression of α2β1-integrins. This suggests that inflammatory mediators such as LTD 4 can be involved in the dissemination and survival of colon cancer cells.