American Association for Cancer Research
Browse

Supplementary Table S1 from Low- and High-Grade Glioma-Associated Vascular Cells Differentially Regulate Tumor Growth

Download (1.23 MB)
dataset
posted on 2024-07-02, 07:40 authored by Sree Deepthi Muthukrishnan, Haocheng Qi, David Wang, Lubayna Elahi, Amy Pham, Alvaro G. Alvarado, Tie Li, Fuying Gao, Riki Kawaguchi, Albert Lai, Harley I. Kornblum

Differentially expressed genes between LG-, PRI- and REC-GVC

Funding

National Institute of Neurological Disorders and Stroke (NINDS)

United States Department of Health and Human Services

Find out more...

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF)

Department of Radiation Oncology, UCLA Health System (Radiation Oncology UCLA)

History

ARTICLE ABSTRACT

A key feature distinguishing high-grade glioma (HG) from low-grade glioma (LG) is the extensive neovascularization and endothelial hyperproliferation. Prior work has shown that tumor-associated vasculature from HG is molecularly and functionally distinct from normal brain vasculature and expresses higher levels of protumorigenic factors that promote glioma growth and progression. However, it remains unclear whether vessels from LG also express protumorigenic factors, and to what extent they functionally contribute to glioma growth. Here, we profile the transcriptomes of glioma-associated vascular cells (GVC) from IDH-mutant (mIDH) LG and IDH-wild-type (wIDH) HG and show that they exhibit significant molecular and functional differences. LG-GVC show enrichment of extracellular matrix–related gene sets and sensitivity to antiangiogenic drugs, whereas HG-GVC display an increase in immune response–related gene sets and antiangiogenic resistance. Strikingly, conditioned media from LG-GVC inhibits the growth of wIDH glioblastoma cells, whereas HG-GVC promotes growth. In vivo cotransplantation of LG-GVC with tumor cells reduces growth, whereas HG-GVC enhances tumor growth in orthotopic xenografts. We identify ASPORIN (ASPN), a small leucine-rich repeat proteoglycan, highly enriched in LG-GVC as a growth suppressor of wIDH glioblastoma cells in vitro and in vivo. Together, these findings indicate that GVC from LG and HG are molecularly and functionally distinct and differentially regulate tumor growth.Implications: This study demonstrated that vascular cells from IDH-mutant LG and IDH-wild-type HG exhibit distinct molecular signatures and have differential effects on tumor growth via regulation of ASPN-TGFβ1-GPM6A signaling.

Usage metrics

    Molecular Cancer Research

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC