Hepatocyte growth factor elevates the activity levels of glycolipid sulfotransferases in renal cell carcinoma cells.

Accumulation of sulfoglycolipids associated with markedly elevated activity levels of glycolipid sulfotransferases has previously been demonstrated in the human renal cell carcinoma cell line, SMKT-R3. To elucidate 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 125I-HGF binding to SMKT-R3 cells indicated that the cells expressed high-affinity receptors for HGF with a Kd of 36 pM and 750 sites/cell. Furthermore, metabolic labeling with [35S]sulfate revealed that the addition of HGF to the culture medium of the cells resulted in an increment of sulfoglycolipid synthesis. Therefore, these observations suggest that HGF can function as a regulatory factor in sulfoglycolipid synthesis through the modulation of the sulfotransferase activity levels in renal cell carcinoma cells. In addition, HGF stimulated the proliferation and motility of SMKT-R3 cells, suggesting that HGF has multiple biological activities in renal cell carcinoma cells.