Transforming Growth Factor β1 Increases the Synthesis and Shedding of the Melanoma-Specific Proteoglycan in Human Melanoma Cells

Melanoma cells produce a cell-specific proteoglycan, mel-PG, which is an integral chondroitin sulfate proteoglycan that can be released into the medium as a result of the proteolytic cleavage of thetrans-membrane form. The effect of transforming growth factor β1 (TGF-β1) on proteoglycan production was studied in three melanoma cell lines at various stages of differentiation: SK-mel-1.36-1-5 (early), SK-mel-3.44 (intermediate), and SK-mel-23 (late). The main effect of TGF-β1 was to increase the synthesis and shedding of mel-PG into the medium without affecting the amount present in the cell membranes nor the balance between the proteoglycan and the glycoprotein forms of mel-PG. After TGF-β1 treatment, there was an increase in the amount of mel-PG present in the medium as observed in metabolic labeling, immunoprecipitation, and pulse–chase experiments. This effect was more pronounced in the SK-mel-1.36-1-5 than in the SK-mel-3.44 cell line, whereas the SK-mel-23 cells did not contain mel-PG either in the presence or in the absence of TGF-β1. Characterization of mel-PG purified from the medium from control and TGF-β1-treated cells showed that the factor increased slightly the GAG chain length in SK-mel-1.36-1-5, but not in SK-mel-3.44 cells, without modifying the degree of sulfation.