Genotechnologic Analysis of Control System of Proliferation and Metastasis by Gangliosides in Melanoma

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We investigated biological functions of gangliosides in melanoma using cell lines and tissue specimens obtained from the patients. SK-MEL-28 (GD3- and GM3-positive cell line) had higher activity of cell proliferation than its GD3-defecient mutant clone. Metastatic melanoma patients with the new ganglioside expression (GM3-predominant) seemed to survive longer than the ones with increased levels of both GM3 and GD3. GD3 was considered to have pivotal parts in concering tumor progression and prognosis. The GD3-deficient cell line, however, showed increased expression of α2β1 and α3β1 integrin receptors and significantly higher ability to adhere to extracellular matrix proteins including type I and IV collagens and laminin than the parent clone (SK-MEL-28). The treatment with monoclonal antibodies against GDs in SK-MEL-28 inhibited the cell attachment to the matrix proteins. Our findings suggest that gangliosides GM3 (by influencing integrin receptor levels) and GD3 (by interacting directly with matrix proteins) might play different biological roles in the progression of melanoma.