Selective increase of α₂-integrin sub-unit expression on human carcinoma cells upon EGF-receptor activation

The effects of chronic EGF exposure on expression of the α₂β₁ collagen and α₅β₁ fibronectin receptor in a pair of human carcinoma cell lines (A431 and A549) with differential responses to EGF in a short-term ECM-cell adhesion assay were investigated. Treatment with EGF at 10 ng/ml for 24 hr increased on both cell lines the expression of the α₂- but not the β₁- or α₅-integrin sub-units, and concomitantly cellular adhesion was increased on collagen IV but not on fibronectin. Increased collagen adhesion of A549 cells could be blocked by α₂- and β₁-integrin-sub-unit antibodies down to control levels, while it was blocked by α₂-integrin-sub-unit antibody only by 60% and completely by the β₁-integrin-sub-unit antibody on A431 cells. EGF induced disparate shifts in cell morphologies (dome-like structures, A431, vs. spindle-like fibroblastoid, A549) with concomitant opposite changes in the expression/localization of E-cadherin in cell-cell contacts. This could be taken as an indication for cell-type-specific differential changes in the ratio of cell-ECM vs. cell-cell contacts. The EGF-induced up-regulation of the α₂β₁ integrin was instrumental in increasing collagen adhesion of A549 but only partly in the case of A431 cells, in which cells the α₂β₁ integrin may have additional functions besides serving as cell-ECM receptor. Int. J. Cancer 80:546–552, 1999. © 1999 Wiley-Liss, Inc.