Vasorin stimulates malignant progression and angiogenesis in glioma

Abstract

Glioma, the most common human primary brain tumor, is characterized by invasive capabilities and angiogenesis. Vasorin (VASN), a transmembrane protein, is reported to be associated with vascular injury repair and is overexpressed in some human tumors. However, its role in tumor progression and angiogenesis in glioma is unknown. In this study, VASN was shown to be overexpressed in high‐grade gliomas, and the expression level correlated with tumor grade and microvessel density in glioma specimens. Glioma patients with high VASN expression had a shorter overall survival time. Knockdown of VASN in glioma cells by shRNA significantly inhibited the malignancy of glioma, including cell proliferation, colony formation, invasion, and sphere formation. Ectopic expression of VASN increased glioma progression in vitro. The expression of VASN correlated with the mesenchymal type of glioblastoma multiforme (GBM) subtyped by gene set enrichment analysis (GSEA). Our results showed that the concentration of VASN was increased in the conditioned medium (CM) from glioma cells with VASN overexpression, and the CM from glioma cells with knockdown or overexpressed VASN inhibited or promoted HUVEC migration and tubulogenesis in vitro, respectively. Glioma growth and angiogenesis were stimulated upon ectopic expression of VASN in vivo. The STAT3 and NOTCH pathways were found to be activated and inhibited by VASN overexpression. Our findings suggest that VASN stimulates tumor progression and angiogenesis in glioma, and, as such, represents a novel therapeutic target for glioma.

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

“…Vasorin (VASN) is a secreted cell surface protein that is associated with vascular injury repair through inhibiting the TGF-β signaling pathway (136), and its overexpression in some human tumors can stimulate malignant progression and angiogenesis (137). In hepatoma, VASN is capable of promoting cell proliferation and migration and inhibiting cell apoptosis and is regarded as a promising biological treatment target for HCC.…”

SIO: A Spatioimageomics Pipeline to Identify Prognostic Biomarkers Associated with the Ovarian Tumor Microenvironment

“…These genes are likely expressed by CD73_1 and CD73_2, two CAF subtypes. Among these genes, CCDC85B , DDAH1 , EFEMP2 , F2RL1 , ITGB1 , LOX , LDLR , MFGE8 , MICAL2 , MKL1 , MSRB3 , NCAM1 , NPTX , PLAT , SLC2A3 , SPSB1 , and VASN have been described as promotors of tumor cell growth, invasion, and migration, as well as angiogenesis [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] ( Table S4, Figure S6 ). HMOX2 , ICMT , MICU1 , and TSPAN9 also positively correlated with CD73_1 and CD73_2 densities and short survival and have been shown to be involved in conferring chemoresistance in ovarian cancer [ 56 , 57 , 58 , 59 ] ( Table S4, Figure S6 ).…”

LRIG3 Suppresses Angiogenesis by Regulating the PI3K/AKT/VEGFA Signaling Pathway in Glioma

“…To further ascertain the most important pathway, we used specific inhibitors to suppress AKT and ERK phosphorylation and found that the AKT, and not the ERK pathway, plays a major role in the LRIG3-modulated VEGFA expression. Activation of the PI3K/AKT pathway in glioma cells can increase VEGFA secretion, both via hypoxia-inducible factor 1 (HIF-1) dependent and independent mechanisms ( 25 , 38 ). Additionally, the PI3K/AKT pathway’s hyperactivation affects numerous biological processes in glioma, including angiogenesis, cytoskeletal rearrangement, cell proliferation, and vasculogenic mimicry formation ( 39 , 40 ).…”