Two types of growth factors have been termed transforming growth factors (TGFs). One of these, TGF-a, is related to epidermal growth factor (EGF) and binds to the EGF receptor, while the other one, TGF-P, is a structurally unrelated protein with a distinct receptor. The initial observation that led to the identification of TGFa was that some retrovirally transformed fibroblasts displayed a strongly reduced number of EGF binding sites at their surface [l]. It was subsequently shown that these cells release an EGF-like factor that is able to bind to the EGF receptors, which then become unavailable for binding of an externally added ligand. This EGF receptor binding factor was first isolated from murine-sarcoma-virus-transformed fibroblast cultures and was therefore initially called sarcoma growth factor [2]. Subsequent examination of a variety of cell sources showed that this factor was made by many more transformed cells but not by adult normal cells in culture [3-61.
Sarcoma growth factor preparations are able to induce profound morphological changes in rat fibroblasts when added to the medium. These changes result in a phenotype similar to that of virally transformed cells. Removal of these growth factor preparations results in a reversion of the cellular phenotype back toward the normal. It was also shown that these preparations enable normal anchorage-dependent rat fibroblasts to grow in soft agar. However, when these anchorage-independent soft agar colonies are selected and subsequently plated in the absence of these growth factor preparations, they grow again as normal contact-inhibited fibroblasts [2,6]. The fact that preparations of this factor were able to convert the normal rat kidney (NRK) cells into phenotypically transformed cells and the synthesis of this factor by several different transformed cells led to the name transforming growth factor.
Initially it was assumed that sarcoma or transforming growth factor was a single peptide [2]. Extensive biochemical purification and characterization showed later that the preparations consisted of the structurally unrelated peptides TGF-a and -j3. While the binding to the EGF receptor is solely due to the presence of TGF-a, the profound morphological changes observed with the rat fibroblasts are due to the cooperative effect of TGF-a and -0 [7]. TGF-P by itself will not induce any colony formation of