The regulatory mechanisms of NG2/CSPG4 expression

Abstract

Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2. These regulatory factors crucially determine NG2-mediated cellular processes such as glial scar formation in the central nervous system (CNS) or tumor growth and metastasis. Therefore, they are potential targets for the establishment of novel NG2-based therapeutic strategies in the treatment of CNS injuries, cancer and other conditions of these types.

Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy Target across Different Tumor Types

“…Although a full understanding of the physiological roles of CSPG4 is still required, all reports suggest it is ubiquitously involved in multiple tissue development and homeostasis processes, and its roles may be differentially modulated based on the nature of the local tissue microenvironment ( 17 ). The regulation of CSPG4 expression is reported to be strongly affected by inflammatory cytokines such as TNF-α, interleukin (IL)-1α, IFN-γ, and TGF-β and hypoxia-induced mechanisms involving hypoxia-inducible factors.…”

The Significance of Chondroitin Sulfate Proteoglycan 4 (CSPG4) in Human Gliomas

“…Although expressed in >50 cell types, including chondroblasts, osteoblasts, keratinocytes, smooth muscle cells, and macrophages [ 49 , 50 ], NG2/CSPG4 expression seems to be confined to precursor or progenitor cells of epithelial and mesenchymal origin [ 48 ]. In particular, NG2/CSPG4 is not expressed by multipotent stem cells, but is upregulated when a stem cell becomes initially committed to a particular cell lineage.…”

Furanodienone overcomes temozolomide resistance in glioblastoma through the downregulation of CSPG4‐Akt‐ERK signalling by inhibiting EGR1‐dependent transcription

“…Although high levels of CSPG4 are frequently used as a marker to identify and predict gliomas, the potential of CSPG4 as a therapeutic target has not been fully explored, and little pharmacologic work has been conducted to elucidate mechanisms regulating its expression (Dawson, Levine, & Reynolds, ). Early studies found that CSPG4 regulated the expression of inflammatory and transcription factors, and these regulatory elements defined CSPG4‐mediated tumourigenesis (Ampofo, Schmitt, Menger, & Laschke, ). Therefore, in anticipation of future therapeutic strategies and developments, the identification of novel agents that can inhibit CSPG4 signalling might be important for the treatment of GBM (Svendsen et al, ; Wang et al, ).…”