Transforming growth factor beta may act as an autocrine-survival-promotingfactor for transformed trophoblasts

Using five trophoblast cell lines of different differentiation status, we h ave shown that trophoblasts could constitutively release the transforming g rowth factor beta-1 (TGF beta1), but not TGF beta2. Treatment of the human tumorigenic, TL, and BeWo cells with a differentiating agent and a potent p rotein kinase C activator-the tumor-promoting agent-or the JEG-3 cells with cholera toxin-a potent cyclic adenosine 3':5'monophosphate (cAMP) inducer- or its analogue 8-bromo-cAMP, potentiates TGF beta production, but the two signaling pathways appear to be mutually exclusive. Surprisingly, the JAR c ell line failed to respond to either type of TGF beta activator. Based on r everse transcriptase (RT)-polymerase chain reaction (PCR), it was found tha t only the JAR cell line expressed messenger ribonucleic acid for decorin, a natural inhibitor of TGF beta, and none of the cell lines had detectable protein expression as determined by immunocytochemical studies. The cell nu mber in cultures with decorin was invariably lesser than in those without d ecorin under serum-free conditions for all the cell. lines tested. These re sults suggest that TGF beta may act as an autocrine-survival factor for tra nsformed trophoblasts by allowing the cells to survive longer under a micro environment which is not favorable for growth. Lastly, our results indicate that decorin, acting in a paracrine manner, may also play an important neg ative regulatory role in the development of transformed trophoblasts by seq uestering TGF beta, thereby preventing its action.