Using five trophoblast cell lines of different differentiation status, we have shown that trophoblasts could constitutively release the transforming growth factor beta-1 (TGFβ1), but not TGFβ2. Treatment of the human tumorigenic, TL, and BeWo cells with a differentiating agent and a potent protein 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 TGFβ production, but the two signaling pathways appear to be mutually exclusive. Surprisingly, the JAR cell line failed to respond to either type of TGFβ activator. Based on reverse transcriptase (RT)-polymerase chain reaction (PCR), it was found that only the JAR cell line expressed messenger ribonucleic acid for decorin, a natural inhibitor of TGFβ, and none of the cell lines had detectable protein expression as determined by immunocytochemical studies. The cell number in cultures with decorin was invariably lesser than in those without decorin under serum-free conditions for all the cell lines tested. These results suggest that TGFβ may act as an autocrine-survival factor for transformed trophoblasts by allowing the cells to survive longer under a microenvironment which is not favorable for growth. Lastly, our results indicate that decorin, acting in a paracrine manner, may also play an important negative regulatory role in the development of transformed trophoblasts by sequestering TGFβ, thereby preventing its action.