Decreased transforming growth factor‐(β) response and binding in insulin‐independent teratoma‐derived cell lines with increased tumorigenic properties

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Abstract
The mouse C3H teratoma‐derived cell line 1246 is an adipogenic cell line which stringently requires insulin to proliferate and differentiate in defined medium. From this cell line an insulin‐independent cell line celled 1246‐3A was isolated. It was found that, in contrast to 1246 cells, 1246‐3A cells had lost the ability to differentiate and became tumorigenic when injected at a density of 106 cells/mouse into syngeneic host C3H mice. In addition, they produce in their culture medium transforming growth factor (α)‐ and (β)‐like polypeptides which stimulate their proliferation. Highly tumorigenic insulin‐independent cell lines able to give rise to tumor when injected at a density of 104 cells/mouse were isolated by using. an in vitro‐in vivo shuttle technique. The highly tumorigenic cell lines have lost the response to TGF‐(β)1, The binding of TGF‐(β)1, to the nontumorigenic parent cell line or to cells displaying increased tumorigenic properties was investigated. The data presented here indicate that the increased tumorigenicity is accompanied by a progressive decrease of specific binding of TGF‐(β)1, to the cells. However, the decreased number of cell surface TGF‐(β)1, binding sites in the highly tumorigenic cells did not correlate with an increase in the secretion of TGF‐(β) protein by the tumorigenic cells, as all of TGF‐(β) produced by the cells was in a latent form. Affinity cross‐linking experiments indicated that the 1246 cell line displayed several TGF‐(β) cross‐linked molecular species (MW 140, 92, and 70 kDa). Increase of tumorigenicity was accompanied by a marked decrease in the intensity of the cross‐linked bands, particularly of the 92 and 70 kDa species.