Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth

Area of Science:

• Neuro-oncology
• Cancer biology
• Vascular biology

Background:

• High-grade gliomas (HG) feature extensive neovascularization, distinct from normal brain vasculature.
• Tumor-associated vasculature in HG promotes glioma growth, but the role of vasculature in low-grade gliomas (LG) is less understood.

Purpose of the Study:

• To compare the molecular and functional characteristics of glioma-associated vascular cells (GVC) from IDH-mutant LG and IDH-wild-type HG.
• To determine the differential impact of LG-GVC and HG-GVC on glioma growth.

Main Methods:

• Transcriptome profiling of GVC from LG and HG gliomas.
• In vitro conditioned media assays using GVC and glioblastoma cells.
• In vivo orthotopic xenograft models with GVC and tumor cell co-transplantation.

Main Results:

• LG-GVC exhibit extracellular matrix gene enrichment and antiangiogenic sensitivity, while HG-GVC show immune response gene enrichment and antiangiogenic resistance.
• Conditioned media from LG-GVC inhibited glioblastoma cell growth, whereas HG-GVC promoted it.
• ASPORIN (ASPN), enriched in LG-GVC, suppressed glioblastoma growth in vitro and in vivo.

Conclusions:

• Glioma-associated vascular cells from LG and HG are molecularly and functionally distinct.
• LG-GVC and HG-GVC differentially regulate tumor growth, with LG-GVC acting as a suppressor and HG-GVC as a promoter.
• ASPN-TGFβ1-GPM6A signaling is implicated in the differential regulation of tumor growth by GVC.