(A) Abrogation of MMP-2 and MMP-9 production in response to fibronectin by high-cell density and its reversion by inhibiting PI-3K and different elements of the Ras/MAPK–signaling pathway. 2 × 10⁷ CEM cells were cultured at a 2 × 10⁵cells/mL or at 1 × 10⁶ cells/mL and exposed to fibronectin. Conditioned medium was obtained after 6 hours, concentrated, and subjected to gelatin zymography. Graph shows the intensity of the gelatinolytic band in untreated cells (baseline), cells expressing Ha-Ras Asn-17, and cells treated with wortmannin, PD 98059, or SB 202190. Concomitant effect on cell binding to fibronectin is also shown. Both adhesion and intensity of the gelatinolytic bands are expressed as fold increase or decrease over that observed with the untreated cells exposed to fibronectin at low density. (B) Effect of cell density on integrin cell-surface expression. Flow cytometry analysis of membrane expression of fibronectin receptors in CEM cells cultured at low density (filled histograms) versus cells cultured at high density (clear histograms). Histograms show fluorescence-intensity distribution among 5 × 10³ cells immunostained with MoAb raised against several integrin  chains and the common β chain.