Specific sialyltransferase is responsible for the synthesis of GD3, a ganglioside preferentially expressed on human metastatic melanoma cells

A number of studies have been directed toward defining surface structures that may be preferentially expressed on human tumor cells of the metastatic phenotype. Human melanoma was used as a tumor model to study the molecular events associated with metastasis. Using monoclonal antibodies directed to a variety of human melanoma associated antigens, they demonstrate that the disialoganglioside GD3 is preferentially expressed on human melanoma cells derived from metastatic foci, whereas cells derived from primary lesions as well as melanocytes express minimal levels of this antigen. The enhanced expression of GD3 on metastatic melanoma cells is due to an increased biosynthetic rate as shown by intrinsic labeling with [3H]-glucosamine. Moreover, they demonstrate the presence of a specific sialyltransferase (GD3 synthetase) responsible for the synthesis of GD3. This enzyme activity is associated with a membrane fraction of human melanoma cells and converts the monosialylated precursor GM3 to GD3. In fact, a cultured human melanoma cell line derived from a metastatic foci was shown to contain a five-fold increase in GD3 synthetase specific activity as compared to that observed for a cell line derived from a primary lesion of the same patient. The elucidation of the mechanism regulating the expression of this enzyme may lead to a more complete understanding of the metastatic phenotype of human melanoma