Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma

Tumor-associated microglia and blood-derived macrophages (TAMs) play a central role in modulating the immune suppressive microenvironment in glioma. Here, we show that GPNMB is predominantly expressed by TAMs in human glioblastoma multiforme and the murine RCAS-PDGFb high grade glioma model. Loss of...

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Published inActa neuropathologica communications Vol. 12; no. 1; p. 50
Main Authors Yalcin, Fatih, Haneke, Hannah, Efe, Ibrahim E, Kuhrt, Leonard D, Motta, Edyta, Nickl, Bernadette, Flüh, Charlotte, Synowitz, Michael, Dzaye, Omar, Bader, Michael, Kettenmann, Helmut
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 02.04.2024
BioMed Central
BMC
Subjects
Analysis
Animals
Brain cancer
Brain Neoplasms - pathology
Brain tumors
Cell Line, Tumor
Database industry
Ethylenediaminetetraacetic acid
Experimental glioma
Gene amplification
Glioblastoma - pathology
Glioma
Glioma - pathology
Gliomas
Glycoproteins
GPNMB
Growth
Growth factors
Humans
Macrophage
Macrophages
Macrophages - metabolism
Medical prognosis
Melanoma
Membrane Glycoproteins - metabolism
Mice
Microglia
Microglia - metabolism
Mouse
Platelet-derived growth factor
Proteins
RCAS
Tumor Microenvironment
Tumors
Germany
United Kingdom > UK
United States > US
GPNMB
Mouse
RCAS
Glioblastoma
Experimental glioma
CD44
Macrophage
Microglia
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Summary:Tumor-associated microglia and blood-derived macrophages (TAMs) play a central role in modulating the immune suppressive microenvironment in glioma. Here, we show that GPNMB is predominantly expressed by TAMs in human glioblastoma multiforme and the murine RCAS-PDGFb high grade glioma model. Loss of GPNMB in the in vivo tumor microenvironment results in significantly smaller tumor volumes and generates a pro-inflammatory innate and adaptive immune cell microenvironment. The impact of host-derived GPNMB on tumor growth was confirmed in two distinct murine glioma cell lines in organotypic brain slices from GPNMB-KO and control mice. Using published data bases of human glioma, the elevated levels in TAMs could be confirmed and the GPNMB expression correlated with a poorer survival.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2051-5960
2051-5960
DOI:10.1186/s40478-024-01754-7