Expression and immunolocalization of Gpnmb, a glioma‐associated glycoprotein, in normal and inflamed central nervous systems of adult rats

Abstract

Glycoprotein nonmetastatic melanoma B (Gpnmb) is a type I transmembrane protein implicated in cell differentiation, inflammation, tissue regeneration, and tumor progression. Gpnmb, which is highly expressed in glioblastoma cells, is a potential therapeutic target. However, little is known about its expression, cellular localization, and roles in non-tumorous neural tissues. In this study, we examined Gpnmb expression in the central nervous system of adult rats under both normal and inflammatory conditions. Reverse transcription-polymerase chain reaction analysis revealed that Gpnmb mRNA was expressed in the cerebrum, cerebellum, brain stem, and spinal cord of normal adult rats. Immunoperoxidase staining revealed that Gpnmb-immunoreactive cells were widely distributed in the parenchyma of all brain regions examined, with the cells being most prevalent in the hippocampal dentate gyrus, cerebellar cortex, spinal dorsal horn, choroid plexus, ependyma, periventricular regions, and in layers II and III of the cerebral cortex. Double immunofluorescence staining showed that these cells were co-stained most frequently with the microglia/macrophage marker OX42, and occasionally with the radial glia marker RC2 or the neuronal marker NeuN. Furthermore, an intraperitoneal injection of bacterial endotoxin lipopolysaccharide increased the number of Gpnmb and OX42 double-positive cells in the area postrema, which is one of the circumventricular organs, indicating infiltration of hematogenous macrophages. These results suggest that Gpnmb, which is expressed in microglia and macrophages in non-tumorous neural tissues, plays an important role in the regulation of immune/inflammatory responses.

Tumor associated seizures in glioblastomas are influenced by survival gene expression in a region-specific manner: A gene expression imaging study

“…GPNMB (glycoprotein nonmetastatic melanoma protein B) encodes for a transmembrane protein implicated in a variety of biological process including cell differentiation, inflammation, tissue regeneration, and invasion and metastasis of malignant tumors (Huang et al, 2012). IGFBP2 encodes insulin-like growth factor-binding protein 2 which inhibits insulin-like growth factor and is overexpressed in glioblastomas (Fukushima and Kataoka, 2007); no definite seizure-related mechanism has been described.…”

Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke

“…GPNMB, (glycoprotein nonmetastatic melanoma protein, also known as osteoactivin) is induced in macrophages by IFN-gamma and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses. This gene was also persistently and strongly upregulated in both age groups, and is amenable to drug manipulation [48]–[50]. Another interesting therapeutic candidate is the pro-inflammatory adipokine gene Cfd which encodes a member of the serine protease family and for which a number of inhibitors exist [51].…”

MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B

“…Glycoprotein non-metastatic melanoma B (GPNMB) is a type I transmembrane protein implicated in various biological processes, such as cell differentiation, inflammation, tissue regeneration, and invasion and metastasis of malignant tumors [8]. Since its initial identification in human melanoma cells, GPNMB has been considered a potential therapeutic target for malignant tumors.…”