Regulation of human (Caco-2) intestinal epithelial cell differentiation by extracellular matrix proteins

Exp Cell Res. 1996 Jun 15;225(2):301-5. doi: 10.1006/excr.1996.0180.


Extracellular matrix regulation of intestinal epithelial differentiation may affect development, differentiation during migration to villus tips, healing, inflammatory bowel disease, and malignant transformation. Cell culture studies of intestinal epithelial biology may also depend on the matrix substrate used. We evaluated matrix effects on differentiation and proliferation in human intestinal Caco-2 epithelial cells, a model for intestinal epithelial differentiation. Proliferation, brush border enzyme specific activity, and spreading were compared in cells cultured on tissue culture plastic with interstitial collagen I and the basement membrane constituents collagen IV and laminin. Each matrix significantly increased alkaline phosphatase, dipeptidyl peptidase, lactase, sucrase-isomaltase, and cell spreading in comparison to plastic. However, the basement membrane proteins collagen IV and laminin further promoted all four brush border enzymes but inhibited spreading compared to collagen I. Proliferation was most rapid on type I collagen and slowest on laminin and tissue culture plastic. Basement membrane matrix proteins may promote intestinal epithelial differentiation and inhibit proliferation compared with interstitial collagen I.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase / drug effects
  • Alkaline Phosphatase / metabolism
  • Caco-2 Cells / cytology*
  • Caco-2 Cells / drug effects
  • Caco-2 Cells / enzymology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Size / drug effects
  • Collagen / pharmacology
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / drug effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
  • Extracellular Matrix Proteins / pharmacology*
  • Humans
  • Laminin / pharmacology
  • Oligo-1,6-Glucosidase / drug effects
  • Oligo-1,6-Glucosidase / metabolism
  • beta-Galactosidase / drug effects
  • beta-Galactosidase / metabolism


  • Extracellular Matrix Proteins
  • Laminin
  • Collagen
  • Alkaline Phosphatase
  • Oligo-1,6-Glucosidase
  • beta-Galactosidase
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases