REGULATION OF HUMAN (CACO-2) INTESTINAL EPITHELIAL-CELL DIFFERENTIATION BY EXTRACELLULAR-MATRIX PROTEINS

Extracellular matrix regulation of intestinal epithelial differentiati on may affect development, differentiation during migration to villus tips, healing, inflammatory bowel disease, and malignant transformatio n. Cell culture studies of intestinal epithelial biology may also depe nd on the matrix substrate used. We evaluated matrix effects on differ entiation and proliferation in human intestinal Caco-2 epithelial cell s, a model for intestinal epithelial differentiation. Proliferation, b rush border enzyme specific activity, and spreading were compared in c ells cultured on tissue culture plastic with interstitial collagen I a nd the basement membrane constituents collagen TV and laminin. Each ma trix significantly increased alkaline phosphatase, dipeptidyl peptidas e, lactase, sucrase-isomaltase, and cell spreading in comparison to pl astic. However, the basement membrane proteins collagen TV and laminin further promoted all four brush border enzymes but inhibited spreadin g compared to collagen I. Proliferation was most rapid on type I colla gen and slowest on laminin and tissue culture plastic. Basement membra ne matrix proteins may promote intestinal epithelial differentiation a nd inhibit proliferation compared with interstitial collagen I. (C) 19 96 Academic Press, Inc.