Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice.

PURPOSE

Heparan sulfate (HS) is one of the factors that has been suggested to be associated with angiogenesis and invasion of glioblastoma (GBM), an aggressive and fast-growing brain tumor. However, it remains unclear how HS of endothelial cells is involved in angiogenesis in glioblastoma and its prognosis. Thus, we investigated the effect of endothelial cell HS on GBM development.

METHODS

We generated endothelial cell-specific knockout of , a gene encoding a glycosyltransferase and essential for HS synthesis, and murine GL261 glioblastoma cells were orthotopically transplanted. Two weeks after transplantation, we examined the tumor progression and underlying mechanisms.

RESULTS

The endothelial cell-specific knockout ( ) mice exhibited reduced HS expression specifically in the vascular endothelium of the brain capillaries compared with the control wild-type (WT) mice. GBM growth was significantly suppressed in mice compared with that in WT mice. After GBM transplantation, the survival rate was significantly higher in mice than in WT mice. We investigated how the effect of fibroblast growth factor 2 (FGF2), which is known as an angiogenesis-promoting factor, differs between and WT mice by using an in vivo Matrigel assay and demonstrated that endothelial cell-specific HS reduction attenuated the effect of FGF2 on angiogenesis.

CONCLUSIONS

HS reduction in the vascular endothelium of the brain suppressed GBM growth and neovascularization in mice.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12672-021-00444-3.