Changing the Nature of Melanoma Cells by Manipulation of Ganglioside Expression

Gangliosides, GSLs that contain sialic acid residues, are components of all animal cell membranes. It was first found by Klenk in 1935. He extracted something of new that was called substance X from the brain of a Niemann–Pick disease patient (Klenk, 1939b). In the following years, he understood (Klenk, 1939a) that substance X was a mixture of compounds and he named them “gangliosides”. Gangliosides attracted immediately the interest of many investigators, but in spite of this, progresses in elucidating their structures were slow. In 1947, the structure of sphingosine was elucidated (Carter et al., 1947) and in 1955 that of sialic acid (Gottschalk, 1955). Finally, in 1963, the first ganglioside structure was described (Kuhn and Wiegandt, 1963). Following studies were extensively devoted to fully understand the ganglioside structural complexity, metabolism, cellular topology, biological functions, and pathobiological implications (Macher and Sweeley, 1978; Miller-Podraza et al., 1992; Sandhoff and Christomanou, 1979; Sandhoff and Conzelmann, 1984; Svennerholm et al., 1994). This research is still far to be considered concluded, but today there is a general agreement to consider gangliosides as functional molecules involved in the modulation of tumor metastasis and of cell signaling, cell invasive proliferation, adhesion, and motility (Bassi et al., 1991; Bremer et al., 1984; Caputto et al., 1977; Chan, 1988; Chan, 1989; Davis and Daly, 1980; Facci et al., 1984; Glebov and Nichols, 2004a; Glebov and Nichols, 2004b; Goldenring et al., 1985; Kim et al., 1986; Kreutter et al., 1987; Leon et al., 1981; Lin and Shaw, 2005; Morgan and Seifert, 1979; Partington and Daly, 1979; Roisen et al., 1981; Rybak et al., 1983; Tsuji et al., 1983; Yates et al., 1989). In particular, systematic analysis of ganglioside antigens in various types of cancer was carried out. In these studies, ganglioside changes were observed based on the comparison of tumor tissues with corresponding normal tissues. Dramatic changes of ganglioside composition and metabolism were first shown using a cultured cell population after viral transformation (Hakomori and Murakami, 1968; Mora et al., 1969). In Balb/c 3T3 cells transformed with Kirsten strain of murine sarcoma virus (the tumor is called 3T3KiMSV), asialo-GM2 (Gg3) is greatly accumulated, with deletion of higher gangliosides. Rabbit