Human enterocyte (Caco-2) migration is modulated in vitro by extracellular matrix composition and epidermal growth factor.

Abstract

The modulation of enterocyte sheet migration was studied using Caco-2 cells, a well-differentiated human colonic cell line. Although Caco-2 cells attached and spread equivalently over collagen types I, III, IV, and V and laminin, migration over laminin was significantly slower than migration over the collagen types. Fibronectin was a poor substrate for attachment, spreading, and migration. Epidermal growth factor (EGF) stimulated migration over laminin but did not alter Caco-2 migration over collagen or fibronectin. This effect was independent of cell proliferation, which was stimulated equivalently on both laminin and collagen I. Expression and organization of cell surface receptors for matrix (integrins) were studied using antibodies specific for f and a integrin subunits. Integrin surface expression was assessed by immunoprecipitation of surface l25i dinated control and EGF-treated cells. fi1 surface pools did not change substantially in any condition studied. al subunit pools were decreased after EGF treatment on collagen I but al pools increased after EGF treatment on laminin. Surface pools of a2 subunits were increased following EGF treatment whether cells were cultured on laminin or collagen I. However, traditional immunofluorescent and laser confocal imaging demonstrated substantial differences in the character of a2 subunit organization between collagen and laminin in the migrating cell front. Furthermore, a functional antibody to the a2 subunit inhibited EGF stimulation of migration over laminin without substantial effects on basal migration over laminin or collagen I. Thus, EGF appears to exert a matrix-specific effect on enterocyte migration by modulation of integrin expression and organization. (J. Clin. Invest. 1992. 90:15-23.)

Novel Roles of Local Insulin-Like Growth Factor-1 Activation in Gastric Ulcer Healing

“…[1][2][3] To determine the role of IGF-1 in cell migration, we examined RGM1 cell migration in scratch wound assay across wound edge after 24-hour treatment with IGF-1 or medium only control. Treatment with IGF-1 at 5, 10, and 50 ng/ml significantly increased the RGM1 cell migration rate by sevenfold, eightfold, and threefold, respectively, compared with controls ( Figure 2, A and B).…”

“…1,2 Growth factors such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) activate epithelial cell migration and proliferation and accelerate ulcer healing in vivo and in vitro by interacting with specific cell surface receptors, which initiate cascades of intracellular events. [1][2][3] Insulin-like growth factor-1 (IGF-1) is a peptide that binds to IGF receptor-1 (IGFR-1), a tyrosine kinase membrane receptor. Activation of IGFR-1 by IGF-1 is implicated in cell survival, growth, differentiation, and migration in epithelial and mesenchymal tissues.…”

Integrins and human intestinal cell functions

“…The alpha2beta1 binding capacity for laminin-1 appears substantially greater than for laminin-2, although much lower than for collagen (108) but recent studies suggest that alpha2beta1 may act in cooperation with alpha6beta4 for attachment to laminin-1 (14). There is also evidence that this receptor may be involved in EGF-mediated Caco-2 cell migration on laminin (109). On the other hand, the promoting effect of TGFalpha on glandular differentiation of SW1222 cells grown in a 3-dimensional collagen gel was shown to be primarily mediated by the alpha2beta1 integrin (110).…”

Amphiregulin acts as an autocrine growth factor in two human polarizing colon cancer lines that exhibit domain selective EGF receptor mitogenesis

“…These ligands have been shown to mediate various cellular functions, including proliferation, differentiation and migration (Basson et al, 1992(Basson et al, , 1994Amemiya et al, 1994;Chen et al, 1994;Traverse et al, 1994). In epithelial cells cultured as a flat monolayer on plastic, it has been shown that TGF-α and AR can act in an autocrine manner (Culouscou et al, 1992;Johnson et al, 1992;Li et al, 1992;Ziober et al, 1993;Qi et al, 1994).…”