SUCRALFATE IMPEDES INTESTINAL EPITHELIAL SHEET MIGRATION IN A CACO-2 CELL-CULTURE MODEL

Sucralfate, which binds to the matrix of the ulcer bed, is theoretical ly advantageous for duodenal ulcer therapy, but has not fulfilled its promise clinically. We examined the effects of sucralfate and related compounds in a human intestinal epithelial (Caco-2) cell culture model of restitution on sheet migration across and adhesion to collagen I. Migration was quantitated across a collagen I matrix treated with sucr alfate or related compounds and correlated with cell adhesion. Caco-2 motility was significantly and dose-responsively inhibited by sucralfa te at therapeutic luminal concentrations. Sucrose octaacetate, the suc ralfate backbone, and lactose octaacetate exhibited similar effects wh ile the beta-bonded disaccharide maltose octaacetate had little effect . Sucrose itself slightly stimulated motility. Adhesion effects parall eled motility. Thus, sucralfate may inhibit intestinal epithelial moti lity by sterically interfering with adhesion to collagen I. A sucralfa te analog with a lactose octaacetate backbone might retain growth fact or binding without inhibiting enterocyte motility, perhaps improving i ts clinical efficacy.