title: Hepatocyte growth factor elevates the activity levels of glycolipid sulfotransferases in renal cell carcinoma cells.
abstract: 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.
authors.affiliation: Biochemistry Laboratory, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Honke
authors.forename: S
authors.initials: S
authors.lastname: Gasa
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
authors.forename: H
authors.initials: H
authors.lastname: Tajima
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Makita
mesh_terms: D000818:Animals; D016466:CHO Cells; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006017:Glycolipids / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000201:enzymology*; D007700:Kinetics; D051379:Mice; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D015238:Sulfotransferases / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D006017:Glycolipids; D006133:Growth Substances; D007106:Immune Sera; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D003513:Cycloheximide; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase