Synthesis and shedding of hyaluronan from plasma membranes of human fibroblasts and metastatic and non-metastatic melanoma cells

The regulation of hyaluronan synthesis and shedding was analysed in human f ibroblasts and in two melanoma cells that differed in the metastatic potent ial and proteolysis of the hyaluronan receptor CD44. Dissociation of nascen t hyaluronan from plasma membranes isolated from fibroblasts by high salt c oncentrations led to activation of hyaluronan synthase. Hyaluronan synthesi s was also enhanced in plasma membranes from fibroblasts that had been trea ted with hyaluronidase or trypsin. Hyaluronan oligosaccharides stimulated h yaluronan production in fibroblast cultures. These results indicated that n ascent high-molecular-mass hyaluronan inhibited its own chain elongation, i f it was retained in the vicinity of the synthase by cell-surface receptors . The results also indicated that increased hyaluronan synthesis and sheddi ng correlated with proteolysis of CD44 on the melanoma cell lines, which ha s been observed by others.