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Regulation of Fibroblast Hepatocyte Growth Factor/Scatter Factor Expression by Human Breast Carcinoma Cell Lines and Peptide Growth Factors¹

Department of Anatomy and Cell Biology and the Lombardi Cancer Center, Georgetown University, Washington, DC 20007 [S. P. S., S. W. B.], and Department of Biology, Faculty of Science, Kyushu University, Fukuoka 812, Japan [T. N.]

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 ß, epidermal growth factor, and transforming growth factor .

¹ Supported in part by a grant from the National Kidney Foundation.

² To whom requests for reprints should be addressed, at Department of Anatomy and Cell Biology, Georgetown University, Medical-Dental Building, 3900 Reservoir Rd., Washington, DC 20007.

Received 8/21/92. Accepted 1/ 8/93.

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