Synthesis and Secretion of Transforming Growth Factor-β1 by Human Desmoid Fibroblast Cell Line and Its Modulation by Toremifene

Abstract

The present study provides evidence that the in vitro cultured fibroblast cell line from desmoid tumors differs from normal fibrobasts in its extracellular matrix (ECM) macromolecule composition and is modulated by treatment with toremifene, an antiestrogen that reduces tumor mass by an unknown mechanism. The results showed increased transforming growth factor-β 1 (TGF-β1) production, TGF-β1 mRNA expression, and TGF-β1 receptor number in desmoid fibroblasts compared with normal cells. As desmoid fibroblasts did not produce tumor necrosis factor-α (TNF-α) but were sensitive to it, which enhanced glycosaminoglycans (GAG) accumulation, we assessed the TGF-β1 effects on TNF-α production by human monocytes. Our results showed TGF-β1 significantly increased TNF-α secretion by monocytes. Toremifene mediated its effects in desmoid fibroblasts via an estrogen receptor-independent pathway. It inhibited GAG accumulation and the secretion of both latent and active forms of TGF-β1 and had an inhibitory effect on TNF-α production by monocytes. Our results suggest that in reducing TGF-β1 production by desmoid fibroblasts and TNF-α production by monocytes, toremifene may restore the balance between the two growth factors.