Regulation of human (Caco-2) intestinal epithelial cell differentiation by extracellular matrix proteins.
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.
Basson
M D
MD
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA. basson.marc_d+@west-haven.va.gov
Turowski
G
G
Emenaker
N J
NJ
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D018938:Caco-2 Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D009834:Oligo-1,6-Glucosidase / Q000187:drug effects / Q000378:metabolism; D001616:beta-Galactosidase / Q000187:drug effects / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D007797:Laminin; D003094:Collagen; D000469:Alkaline Phosphatase; D009834:Oligo-1,6-Glucosidase; D001616:beta-Galactosidase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases