Regulation of fibroblast hepatocyte growth factor/scatter factor expression by human breast carcinoma cell lines and peptide growth factors.

Hepatocyte growth factor/scatter factor (HGF/SF) is a stromally derived modulator of epithelial cell proliferation and morphology. To better assess the potential role of HGF/SF in tumor progression we sought to identify factors and biological conditions which regulate its expression. We show that several adult human primary fibroblast cultures from breast and prostate produce HGF/SF. HGF expression in the MRC-5 human fetal lung fibroblast cell line is stimulated by conditioned media harvested from human breast tumor cell lines (MCF-7, T47D, and MDA-MB-231). In contrast, both indirect and direct coculture of each of these tumor lines with MRC-5 fibroblasts down-regulates HGF/SF expression. Finally, we show that MRC-5 HGF expression is inhibited by several known peptide growth factors, including transforming growth factor beta, epidermal growth factor, and transforming growth factor alpha.