We demonstrated previously (S. Kawamura et al., Int. J.
Cancer, 94: 343-347, 2001) that large amounts of
ganglioside G(M3) accumulate in superficial
bladder tumor, compared with invasive
bladder tumors and that exogenous G(M3) inhibits the invasive potential of
bladder tumor cells. To apply the G(M3) overexpression system to
bladder tumor therapy, direct evidence for the important role of G(M3) in
bladder tumor invasion must be obtained through transfer of the gene responsible for G(M3) overexpression. To determine the most appropriate
cancer cell line for elucidating the antitumor effect of
ganglioside G(M3) overexpression, the present study examined
glycolipid composition,
enzyme activity, and
mRNA expression of the
glycosyltransferases responsible for G(M3) synthesis in the
bladder tumor cell lines KK-47, J82, MGH-UI, YTS-1, and MBT-2. A murine bladder
carcinoma cell line (MBT-2) was transfected with a G(M3) synthase [(
lactosylceramide alpha2,3-N-acetyl
sialic acid transferase);
sialyltransferase-I; SAT-I]
cDNA, because this line does not naturally express G(M3). Stable transfectants (MBT-2-SAT-I) that overexpressed G(M3) were characterized by a reduced potential for cell proliferation, motility, invasion, and xenograft
tumor growth, and an increase in the number of apoptotic cells. In the proportion of synthetic S phase, cells did not differ between MBT-2-SAT-I and mock-transfectant cells. These results suggest that the decreased proliferative potential related to G(M3) overexpression was attributable to the increased number of apoptotic cells. Although details of the mechanism of apoptosis remain unclear, the overexpression of G(M3) by gene transfer of SAT-I may present a novel therapeutic modality.