Accumulation of
sulfolipids associated with markedly elevated levels of
glycolipid sulfotransferase activities was previously demonstrated in human
renal cell carcinoma cells. To explore the regulation mechanisms of sulfoglycolipid synthesis in
renal cancer, effects of various
growth factors on the metabolic
enzymes of
sulfoglycolipids were investigated by using a human
renal cell carcinoma cell line, SMKT-R3. Among the
growth factors tested,
transforming growth factor alpha (
TGF-alpha) and
epidermal growth factor (
EGF) were found to increase the
sulfotransferase activity markedly (about 300%), but did not change that of
arylsulfatase A, which hydrolyzes
sulfoglycolipids. The augmented effects of
TGF-alpha was abolished by
cycloheximide. Since
TGF-alpha is known to bind to the same receptor as
EGF, SMKT-R3 cells were investigated for the
EGF receptor by affinity cross-linking with 125I-EGF. A radiolabeled
protein with a molecular mass of 175 kDa corresponding to the
ligand-receptor complex was immunoprecipitated with a monoclonal anti-
EGF receptor antibody. When production of the
growth factors was examined immunochemically, the cells were found to secrete
TGF-alpha at a low level and retain it in a membrane-bound form, whereas
EGF was not detected. These observations suggest that the
sulfotransferase activities are regulated through the autocrine, paracrine, and/or juxtacrine modes of intercellular stimulation by
TGF-alpha in human
renal cancer cells.