Synthesis and secretion of transforming growth factor-beta 1 by human desmoid fibroblast cell line and its modulation by toremifene

The present study provides evidence that the in vitro cultured fibroblast c ell line from desmoid tumors differs from normal fibrobasts in its extracel lular matrix (ECM) macromolecule composition and is modulated by treatment with toremifene, an antiestrogen that reduces tumor mass by an unknown mech anism. The results showed increased transforming growth factor-beta1 (TGF-b eta1) production, TGF-beta1 mRNA expression, and TGF-beta1 receptor number in desmoid fibroblasts compared with normal cells. As desmoid fibroblasts d id not produce tumor necrosis factor-alpha (TNF-alpha) but were sensitive t o it, which enhanced glycosaminoglycans (GAG) accumulation, we assessed the TGF-beta1 effects on TNF-alpha production by human monocytes. Our results showed TGF-beta1 significantly increased TNF-alpha secretion by monocytes. Toremifene mediated its effects in desmoid fibroblasts via an estrogen rece ptor-independent pathway. It inhibited GAG accumulation and the secretion o f both latent and active forms of TGF-beta1 and had an inhibitory effect on TNF-alpha production by monocytes. Our results suggest that in reducing TG F-beta1 production by desmoid fibroblasts and TNF-alpha production by monoc ytes, toremifene may restore the balance between the two growth factors.