Abstract

We have examined whether the extracellular matrix is a biochemical target for transforming growth factor-beta (TGFbeta). We find that TGFbeta increases the expression of the major extracellular matrix proteins, fibronectin and collagen. This effect is a general response to TGFbeta seen in primary cultures and established lines of cells from various types, normal and transformed. The relative incorporation of fibronectin and collagen into the matrix also increases in response to TGFbeta. The effect of TGFbeta on fibronectin levels as characterized in chick embryo fibroblasts is rapid, selective, persistent, and specific, and involves transcriptional events; it is not mimicked by other growth factors tested. The induction of anchorage-independent growth of normal fibroblasts by TGFbeta is mimicked by fibronectin and is specifically blocked by inhibitors of fibronectin binding to its cell surface receptor. The results demonstrate a functional involvement of fibronectin in mediating cellular responses to TGFbeta, and suggest a model for TGFbeta action based on the control of the extracellular matrix in target cells.