Ganglioside GD3/GD2 are over-expressed in various neuroectoderm-derived
tumors. Previous studies indicated that GD3 is involved in the enhancement of
cancer properties such as rapid growth and increased invasiveness. However, little is known about the functions of GD3/GD2 in
glioma cells and
glioma microenvironments. To clarify the functions of GD3/GD2 in
gliomas, we used a mouse
glioma model based on the RCAS/Gtv-a system. At first, we compared the
gliomas size between wild-type (WT) and GD3 synthase (GD3S) knockout (KO) mice, showing a less malignant histology and slower
tumor growth in GD3S-KO mice than in WT mice. Immunohistochemistry of
glioma sections from WT and GD3S-KO mice revealed that reactive microglia/macrophages showed different localization patterns between the two genetic types of mice. CD68+ cells were more frequently stained inside
glioma tissues of GD3S-KO mice, while they were stained mainly around
glioma tissues in WT mice. The number of CD68+ cells markedly increased in
tumor tissues of GD3S-KO mice at 2 weeks after injection of transfectant DF-1 cells. Furthermore, CD68+ cells in GD3S(-/-)
glioma tissues expressed higher levels of
inducible nitric oxide synthase. We observed higher expression levels of pro-inflammatory
cytokine genes in primary-cultured
glioma cells of WT mice than in GD3S-KO mice.
DNA microarray data also revealed differential expression levels of various
cytokines and
chemokines in
glioma tissues between WT and GD3S-KO mice. These results suggest that expression of GD3S allows
glioma cells to promote polarization of microglia/macrophages towards M2-like phenotypes by modulating the expression levels of
chemokines and
cytokines.