G_M3 inhibits murine MBT-2 tumor invasion and growth

G_M3 has some important roles in cell-to-cell interaction and has proved to have an optimal concentration for fibronectin mediated cell adhesion. G_M3 content in murine bladder tumor (MBT-2) assessed by thin-layer chromatography was similar to human invasive bladder tumor. From glycolipid composition also, MBT-2 is considered as an appropriate model for human invasive bladder tumor. Anti-tumor effect of locally administered G_M3 on MBT-2 tumor was investigated. MBT-2 cells were injected subcutaneously into the right hind limb of CH3/HeSlc female mice on day 1. Tumor bearing mice were randomly placed on day 8 into G_M3 treatment, G_D3 treament, sialic acid treament and control groups. G_M3 was administered between tumor and fascia at 10 μg in 0.1 ml, 1 μg in 0.1 ml from day 8 to day 20 every other day, 7 times in total. Control group was given 0.1 ml of saline. G_D3 group was given 12.5 μg of G_D3, and sialic acid group 2.5 μg of sialic acid. The relative growth rates of control group, G_M3 1 μg group, G_M3 10 μg group on day 22 were 139±74, 56±39, 22±14, respectively, and statistically significant among these three groups (Mann-Whitney's U test p<0.01). There were no significant difference between control and G_D3 or sialic acid group. All of the 15 control mice had muscle invasion, however, of the 19 G_M3 10 μg administered mice, only 4 had muscle invasion. The incidence of muscle invasion between these 2 groups was statistically significant in χ² test (p<0.001). Locally administered G_M3 inhibited both invasion and growth of MBT-2 tumor. This mechanism could be explained by an important role of G_M3 in cell adhesion mediated by integrin and fibronectin interaction. These results may be applied to antiadhesion therapy of human invasive bladder tumor.