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

Abstract

Type .8 transforming growth factor 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-/3 for NRK fibroblasts). We now show that the response of cells to TGF-,8 is bifunctional, in that TGF-IJ 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-fJ at concentrations in the same range as those that stimulate colony formation of NRK fibroblasts (average ED50 = 10-30 pM TGF-36 for inhibition). Whereas epidermal growth factor and TGF-. 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-(3 is further demonstrated in Fischer rat 3T3 fibroblasts transfected with a cellular myc gene. In these cells TGFf3 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-8 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.

Effect of PDGF and TGF‐β on the release of biogenic amines from invertebrate immunocytes and their possible role in the stress response

“…[9]. Indeed, TGF-ß stimulates the growth of some fibroblasts in the presence of PDGF, while the action is reversed in the presence of epidermal growth factor [10]. Moreover, PDGF acts in synergy with TGF-ß in stimulating DNA synthesis in sparse cultures of human embryonic fibroblasts [11].…”

Bacterial cell wall-induced immunosuppression. Role of transforming growth factor beta.

“…These in situ data support the in vitro evidence that the macrophages are the primary source of the suppressor activity and that this suppressor activity can be attributed, at least in part, to TGFR . Discussion TGF R has recently been shown to be a bifunctional regulator of various cellular and immunologic functions (23). TGF0 can both activate (16) and inhibit (22,(24)(25)(26)(27)(28) immune cell function .…”

The ecology of brain tumors: lessons learned from neurofibromatosis-1

“…Matrix metalloproteinases secreted from these cancer-associated fibroblasts change the ECM and alter the signal transduction responses of epithelial cells to growth factors, thus forming a reactive stroma that enhances tumorigenesis (Lee and Streuli, 1999;Sternlicht et al, 1999). One of the key signaling molecules produced by cancer-associated fibroblasts is transforming growth factor-b (TGF-b): TGF-b activates fibroblasts to increase ECM formation (Keski-Oja et al, 1988) and promotes epithelial cell and fibroblast proliferation, depending upon the complement of growth factors present in the local microenvironment (Roberts et al, 1985). Collectively, these studies support a model of tumorigenesis in which TGF-b signaling creates a permissive stromal state for epithelial cancer initiation and progression (Bhowmick et al, 2004;Cheng et al, 2005).…”