Extracellular matrix (ECM) modulates the EGF-induced migration of liver epithelial cells in serum-free, hormone-supplemented medium.

The influence of the extracellular matrix (ECM) glycoproteins collagen IV, laminin (LN), and fibronectin (FN) on the in vitro migration of epithelial cells was studied using the ECM migration track method (4) with preparations immunostained for LN and FN. The locomotion of rat liver epithelial cells stimulated to migrate in serum-free medium by epidermal growth factor (EGF) in the presence of insulin is inhibited by substratum-bound FN. The inhibition is concentration-dependent up to 0.7 microgram of the protein per cm2. Neither LN nor collagen IV decreased the number of migrating cells, indicating that the inhibition is a specific effect of fibronectin. The data also indicate that the FN-mediated inhibition of migration is an additional and not alternative mechanism to the well-established contact inhibition of locomotion (1) which also occurs in liver epithelial cell cultures. The system is being used for a further analysis of the factors that influence migration of normal and neoplastic epithelial cells and the biochemical mechanisms underlying the migration reaction.