RESTITUTION AT THE CELLULAR-LEVEL - REGULATION OF THE MIGRATING PHENOTYPE

Intestinal epithelial cells migrating across a mucosal defect are gene rally described as dedifferentiated, a term that suggests a loss of re gulatory biology. Since cell biology may be more readily studied in es tablished cell lines than in vivo, a model is developed using the huma n Caco-2 intestinal epithelial cell migrating across matrix proteins. This resembles in vivo models of mucosal healing in its sheet migratio n and loss of the brush border enzymes, which are conventional markers for intestinal epithelial differentiation. Immunohistochemical studie s of migrating Caco-2 cells suggest, however, that the rearrangements of cytoskeletal, cell-cell and cell-matrix proteins during migration a re not random but seem adapted to the migratory state. Indeed, Caco-2 migration may be substantially regulated by a variety of physiologic a nd pharmacologic stimuli and differentiation, measured by the specific activity of the intestinal epithelial brush border enzymes alkaline p hosphatase and dipeptidyl dipeptidase, may be independently pharmacolo gically programmed during the stimulation or inhibition of cell motili ty.