Restitution at the cellular level: regulation of the migrating phenotype

Intestinal epithelial cells migrating across a mucosal defect are generally described as dedifferentiated, a term that suggests a loss of regulatory biology. Since cell biology may be more readily studied in established cell lines than in vivo, a model is developed using the human Caco-2 intestinal epithelial cell migrating across matrix proteins. This resembles in vivo models of mucosal healing in its sheet migration and loss of the brush border enzymes, which are conventional markers for intestinal epithelial differentiation. Immunohistochemical studies of migrating Caco-2 cells suggest, however, that the rearrangements of cytoskeletal, cell-cell and cell-matrix proteins during migration are not random but seem adapted to the migratory state. Indeed, Caco-2 migration may be substantially regulated by a variety of physiologic and pharmacologic stimuli and differentiation, measured by the specific activity of the intestinal epithelial brush border enzymes alkaline phosphatase and dipeptidyl dipeptidase, may be independently pharmacologically programmed during the stimulation or inhibition of cell motility.