Type beta transforming growth factor: a bifunctional regulator of cellular growth.

TLDR

TGF‑β is a 25‑kDa two‑chain polypeptide isolated from various tissues that stimulates reversible transformation of nonneoplastic murine fibroblasts, as shown by colony formation in soft agar with an ED50 of 4 pM. TGF‑β exerts a bifunctional effect, inhibiting both anchorage‑dependent and anchorage‑independent growth of various fibroblast and tumor cell lines at low picomolar concentrations, while its interaction with other growth factors (EGF, PDGF) can be synergistic or antagonistic depending on the cell context, indicating that its cellular effects depend on the repertoire of growth factors and receptors present.

Abstract

Type beta transforming growth factor (TGF-beta) is a two-chain polypeptide of 25,000 daltons isolated from many tissues, including bovine kidney, human placenta, and human platelets. It has been characterized by its ability to stimulate reversible transformation of nonneoplastic murine fibroblasts, as measured by the formation of colonies of these cells in soft agar (ED50 = 4 pM TGF-beta for NRK fibroblasts). We now show that the response of cells to TGF-beta is bifunctional, in that TGF-beta inhibits the anchorage-dependent growth of NRK fibroblasts and of human tumor cells by increasing cell cycle time. Moreover, the anchorage-independent growth of many human melanoma, lung carcinoma, and breast carcinoma cell lines is inhibited by TGF-beta at concentrations in the same range as those that stimulate colony formation of NRK fibroblasts (average ED50 = 10-30 pM TGF-beta for inhibition). Whereas epidermal growth factor and TGF-beta synergize to induce anchorage-independent growth of NRK fibroblasts, their effects on the growth of A-549 human lung carcinoma cells are antagonistic. The bifunctional response of cells to TGF-beta is further demonstrated in Fischer rat 3T3 fibroblasts transfected with a cellular myc gene. In these cells TGF-beta synergizes with platelet-derived growth factor to stimulate colony formation but inhibits the colony formation induced by epidermal growth factor. The data indicate that the effects of TGF-beta on cells are not a function of the peptide itself, but rather of the total set of growth factors and their receptors that is operant in the cell at a given time.