Iron saturation alters the effect of lactoferrin on the proliferation and differentiation of human enterocytes (Caco-2 cells).

Recent studies have indicated that lactoferrin may act as a cell mitogen. The effect of human and bovine lactoferrins on the proliferation and differentiation of a human intestinal epithelial cell line (Caco-2) was investigated and compared with that of human transferrin. Caco-2 cells were cultured in serum-free media supplemented with both iron-unsaturated and -saturated forms of the iron-binding proteins. Cell proliferation and differentiation were evaluated by examining growth curves and measuring sucrase and alkaline phosphatase activities of brush border membrane fractions, respectively. The iron-binding status of lactoferrins and transferrin affected the proliferation of Caco-2 cells. The iron-saturated forms of human (S-hLf), bovine (S-bLf) lactoferrins and human transferrin (S-hTf) enhanced cell proliferation, while iron-unsaturated forms (U-hLf, U-bLf, and U-hTf) suppressed it. Iron-binding status also determined the effect of lactoferrin and transferrin on cellular differentiation, but this effect differed for different brush border enzymes. S-hTf enhanced sucrase activity more than S-hLF or S-bLf. Both U-hLf and U-bLf markedly suppressed sucrase activity. U-hTf suppressed alkaline phosphatase activity appreciably, while the other iron-binding proteins showed no significant effect on it. Lactoferrin and transferrin may modulate the proliferation and differentiation of intestinal epithelial cells, but their efficacy depends on their saturation with iron.