EXTRACELLULAR HETEROTRIMERIC LAMININ PROMOTES DIFFERENTIATION IN HUMAN ENTEROCYTES

To investigate the role of laminin (Ln) and merosin (a Ln variant) in the modulation of intestinal epithelial cell differentiation, we have analyzed their functional expression as well as their potential influe nce during the differentiation process of Caco-2 cells, a human cell l ine unique in its property to differentiate into a mature enterocyte-l ike cell type in vitro. By indirect immunofluorescence and Western blo tting, Caco-2 cells have been found to express the B-1 and B-2 chains of Ln, as well as a heavy similar to 350- to 370-kDa chain related to the human A chain, but not the M chain, of merosin. A gradual depositi on of this A-like chain-containing Ln molecule has been observed as Ca co-2 cells undergo differentiation. At the cellular level, a clear rel ationship between basal staining for the A chain and apical staining f or the brush-border membrane enzyme sucrase-isomaltase (SI) has been o bserved. Human Ln, used as substratum, has been found to increase sign ificantly the expression of SI and lactase in Caco-2 cells, whereas bo th Ln and human merosin have been shown to stimulate aminopeptidase N and alkaline phosphatase expression. Taken together, these data indica te that enterocytic differentiation-related gene expression is promote d by an extracellular deposition of Ln and may be susceptible to a dif ferential modulation by variant forms of the molecule.