HEPATOCYTE GROWTH-FACTOR SPECIFICALLY BINDS TO SULFOGLYCOLIPIDS

Hepatocyte growth factor (HGF) is a heparin-binding pleiotropic factor that acts on a variety of epithelial cells. The interaction of human HGF with glycolipids was studied by overlaying them with I-125-HGF on thin layer chromatograms and by a solid-phase assay using lipids adsor bed on microtiter plates. Among various glycolipids tested, HGF was fo und to bind to sulfoglycolipids, including galactosylceramide sulfate (SM4), lactosylceramide sulfate (SM3), and gangliotriaosylceramide bis -sulfate. In contrast, HGF failed to bind to gangliosides or neutral g lycolipids. HGF binding to SM4 was strongly inhibited by dextran sulfa te, heparin, and fucoidan, whereas neither keratan sulfate nor hyaluro nic acid had any inhibitory activity. When glycolipids from a renal ca ncer cell line, SMKT-R3, which overexpresses sulfoglycolipids, were de veloped on a thin layer chromatogram, SM4 and SM3 were the only glycol ipids that bound HGF. We further examined the effect of the incorporat ion of glycolipids into SMKT-R3 cells on HGF binding to the cells. The incorporation of SM4 into the cells enhanced HGF binding to SMKT-R3 c ells, while that of galactosylceramide, a precursor of SM4, had no eff ect. These observations indicated that SM4 exogenously incorporated in to the cell membranes could react with HGF and suggested that endogeno us sulfoglycolipids on SMKT-R3 cells might function as reservoirs for HGF.