HEPATOCYTE GROWTH-FACTOR ELEVATES THE ACTIVITY LEVELS OF GLYCOLIPID SULFOTRANSFERASES IN RENAL-CELL CARCINOMA-CELLS

Accumulation of sulfoglycolipids associated with markedly elevated act ivity levels of glycolipid sulfotransferases has previously been demon strated in the human renal cell carcinoma cell Line, SMKT-R3. To eluci date the regulatory mechanisms of sulfoglycolipid synthesis in SMKT-R3 cells, the effects of various growth factors on the metabolic enzymes of sulfoglycolipids were investigated. Hepatocyte growth factor (HGF) significantly increased the activity levels of the sulfotransferases in a dose-dependent manner, but did not change that of arylsulfatase A , which hydrolyzes sulfoglycolipids. Scatchard analysis of I-125-HGP b inding to SMKT-R3 cells indicated that the cells expressed high-affini ty receptors for HGF with a K-d of 36 pM and 750 sites/cell. Furthermo re, metabolic labeling with [S-35]sulfate revealed that the addition o f HGF to the culture medium of the cells resulted in an increment of s ulfoglycolipid synthesis. Therefore, these observations suggest that H GF can function as a regulatory factor in sulfoglycolipid synthesis th rough the modulation of the sulfotransferase activity levels in renal cell carcinoma cells. In addition, HGF stimulated the proliferation an d motility of SMKT-R3 cells, suggesting that HGF has multiple biologic al activities in renal cell carcinoma cells.