Ehrlich ascites tumor cells produce a transforming growth factor-beta (TGF beta)-like activity but lack receptors with TGF beta-binding capacity

Ehrlich ascites tumor cells incorporate [methyl-H-3]thymidine into DNA independently of exogenous growth factors or fetal calf serum. Using an acid/ethanol extraction procedure we have obtained from these tumor cells a fraction that induces both the proliferation and the formation of cell foci by Swiss 3T3 mouse fibroblasts in the presence of insulin; inhibits the proliferation of Mv1Lu mink lung epithelial cells; and stimulates the growth of NRK rat kidney fibroblasts in soft-agar in the presence of epidermal growth factor. An antibody against transforming growth factor-beta (TGF beta) prevents both the tumor extract-induced proliferation of Swiss 3T3 fibroblasts and the tumor extract-induced proliferative arrest of Mv1Lu cells. The tumor cells secrete a TGF beta-like activity to the extracellular medium in a partially-activated form. However, authentic TGF beta does not affect their proliferation, and no TGF beta receptors were detected using [I-125]TGF beta as a ligand. Therefore, the absence of TGF beta receptors with ligand-binding capacity in these tumor cells may bypass the negative control that this factor exerts on the proliferation of their normal cell counterparts.