12-O-tetradecanoylphorbol-13-acetate-induced changes in sulfated proteoglycan synthesis in cultured chondroblasts

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) rapidly blocks the terminal differentiation of normal cultured chondroblasts. In TPA, the chondroblasts lose their characteristic polygonal morphology and initiate the synthesis of an atypical type IV sulfated proteoglycan. This atypical proteoglycan has lower molecular size, shorter polysaccharide chains, and different 4S-disaccharide:6S-disaccharide ratio in comparison with type IV sulfated proteoglycan from untreated chondroblasts. When removed from TPA, the cells reacquire their characteristic polygonal morphology and reinitiate the synthesis of their typical cartilage-characteristic type IV sulfated proteoglycan. TPA has no readily detectable effect on the type III sulfated proteoglycan synthesized by fibroblasts.