SoxF transcription factors in tumor angiogenesis

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive and vascularized malignant brain tu-mor. Anti-VEGF therapy is widely used for the treatment of GBM, however it has shown only minor impact on patient survival. Thus, more precise molecular mechanisms for glioma angiogenesis are needed for the advance in the treatment of GBM. Here, I investigated the roles of endothelium specific transcription factors Sox7 and Sox17 in the angiogenesis of GL261 murine glioma model. Unlike ectopic LLC tumor, endothelial cell specific Sox17 deletion induced glioma angiogenesis and vascular destabilization. However, Sox7 deletion reduced glioma angiogenesis and stabilized tumor vasculature. The Notch ligand Dll4 induced Sox7 expression via Sox17 downregulation in high-grade glioma. Sox7 promoted but Sox17 repressed the expression of VEGFR2 in glioma vessels. Sox7 deletion also induced the recruitment of effector $CD8^+$ T cells and reduction of regulatory T cells in glioma-bearing mouse brain. Together, Sox7 and Sox17 have opposing roles in glioma angiogenesis and they are key regulators of glioma progression and microenvironment.