Substrate-dependent effect of epidermal growth factor on intercellular adhesion and synthesis of triton-insoluble proteins in human carcinoma A431 cells.

Human epidermoid carcinoma A431 cells attach more rapidly to collagen type-I and -IV substrates than to surfaces coated with laminin or fibronectin. The diminished intercellular interaction and rounding up manifested when these cells are exposed to epidermal growth factor (EGF) in tissue culture plastic or collagen films is not shown when the assay is performed on 3-dimensional collagen. In the latter substrate, cells exposed to EGF reveal greater cell cohesion with interdigitations and desmosomal junctions, compared to the limited intercellular interaction detected in similarly treated cells assayed in tissue culture substrate. Although the protein synthesis inhibitor, cycloheximide, did not prevent these EGF-mediated changes, metabolic labelling indicated a substrate-dependent effect of EGF on the synthesis of proteins associated with the Triton-insoluble cytoskeletal matrix. The involvement of cytoskeleton components in the EGF effects on intercellular adhesion was shown by its susceptibility to cytochalasin B, known to disorganize actin-containing microfilaments. Some of the mechanisms of epithelial morphogenesis and the influence of extracellular matrix components on cell-receptor/growth-factor interactions may now be suitably analyzed by examining the EGF effects on A431 cells grown on different substrata.