Functional Analysis of Ganglioside-Respondable Human Neuroblastoma Cell Lines

Abstract

Previous reports from our laboratory (Tsuji et al., 1983) showed that ganglioside GQlb is capable of promoting cell proliferation, neurite number and neurite length in a highly specific manner in two human neuroblastoma cell lines, GOTO and NB-1. As little as a few nanomolar concentration of GQlb was sufficiently effective. Our subsequent analysis of the structure and activity relationship using various gangliosides revealed an interesting fact that two disialosyl residues of GQlb structure are absolutely necessary for the expression of the activity (Nakajima et al., 1986). As seen in Table 1, in which the results of the analysis are summarized schematically, any deletion of one sialic acid from either disialosyl residue results in complete loss of activity and the mere existence of four sialic acid residues does not assure the activity (e.g., compare with GQlc). Thus, the mode of action of GQlb is quite specific. The significance of this two disialosyl structure will be discussed again later. Furthermore, it was found that GQlb-oligosaccharide, which was prepared from GQ1b by the ozonolysis method (Wiegandt and Backing, 1970), could reproduce the activity but only at a 100 times the concentration of GQ1b itself, and that its maximal activity to be attained remained half as much as that of GQ1b (Nakajima et al., 1986). This fact implies an important role not only of the oligosaccharide portion of GQlb but also of its ceramide portion, particularly in support of its possible involvement in the structure and function of the cell membrane.