Epidermal growth factor receptor ligands are chemoattractants for normal human mesothelial cells

Signalling through epidermal growth factor (EGF) receptor leads to several cellular responses including cell division and cell migration. Since EGF receptors are expressed on normal mesothelial cells, this study investigated whether EGF receptor ligands act as chemoattractants on these cells. The study used Boyden chambers fitted with filters coated with the adhesive matrix proteins fibronectin, laminin, collagen type IV and the nonmatrix adhesive molecule poly-L-lysine, for the migration studies. Normal mesothelial cells migrated to EGF receptor ligands such as EGF, transforming growth factor (TGF)-alpha and heparin-binding epidermal growth factor (HB-EGF) at concentrations ranging,0.024-100 ng.mL(-1) (with a peak stimulation at 6.25 ng.mL(-1)), if matrix proteins were present as adhesive substrates. This migration was integrin-dependent since the same cells failed to migrate in the absence of extracellular matrix molecules or when the Boyden chamber assay was performed in the presence of anti-beta(1) integrin monoclonal antibodies. These findings describe for the first time epidermal growth factor receptor ligands acting as chemoattractants on normal mesothelial cells, and that signalling through epidermal growth factor receptors leading to mesothelial cell migration also requires the activation of integrins.