Insufficient TGF-beta 1 production inactivates the autocrine growth suppressive circuit in human ovarian cancer cell lines

TGF-beta 1 is a secreted polypeptide that elicits an antiproliferanve respo nse in many cell types. However; many epithelial cancer cell lines are resi stant to TGF-beta 1 growth inhibition We investigated the in vitro growth s uppressive effect of TGF-beta 1 on five ovarian cancer cell lines. Two of t hese (OVCAR-3 and AZ364) were growth inhibited by TGF-beta 1. The other thr ee cell lines (SKOV-3, AZ224 and AZ547), were resistant to the antiprolifer ative action of the cytokine. All five cell lines produce TGF-beta 1 mRNA a t very different levels and also secrete the TGF-beta 1 polypeptide, but ma inly in a biologically Intent form as tested by ELISA; this probably explai ns the fact that the TGF-beta 1 autocrine growth inhibition circuit is not active, even in sensitive cell lines. Even complete activation of the in vi tro secreted latent form would be insufficient to induce growth arrest when compared to the levels of exogenous TGF-beta 1 needed to induce growth arr est in sensitive cell lines. The TGF-beta 1 receptor type I mRNA is express ed by all five ovarian cancer cell lines, brit two of them (A2224 and AZ547 ) lack detectable TGF-beta 1 receptor type II mRNA expression. Since TGF-be ta 1 signaling requires both receptor types, the lack of receptor type II i n two cell lines may explain their resistance to growth inhibition. Further experiments should be carried out on receptors and downstream components t o pinpoint the cause of resistance in the SKOV cell line.