Sustained down-regulation of the epidermal growth factor receptor by decorin - A mechanism for controlling tumor growth in vivo

The small leucine-rich proteoglycan decorin interacts with the epidermal gr owth factor receptor (EGFR) and triggers a signaling cascade that leads to elevation of endogenous p21 and growth suppression. We demonstrate that dec orin causes a sustained down-regulation of the EGFR. Upon stable expression of decorin, the EGFR number is reduced by similar to 40%, without changes in EGFR expression. However, EGFR phosphorylation is nearly completely abol ished. Concurrently, decorin attenuates the EGFR-mediated mobilization of i ntracellular calcium and blocks the growth of tumor xenografts by down-regu lating the EGFR kinase in vivo. Thus, decorin acts as an autocrine and para crine regulator of tumor growth and could be utilized as an effective antic ancer agent.