Molecular profiling of the tumor microenvironment in glioblastoma patients: correlation of microglia/macrophage polarization state with metalloprotease expression profiles and survival.

Abstract:

:Due to poor prognosis of glioblastoma (GBM), there is an urgent need to develop new therapeutic strategies. Besides eliminating GBM tumor cells and stem cells, a novel therapeutic approach aims to target Glioma-associated microglia/macrophages (GAMs). We investigated the molecular profile of GAMs correlated with patient prognosis by exploiting M1/M2-like polarization markers in a cohort of 20 GBM patients. Using quantitative PCR (qPCR), the markers CXCL10 (M1) and CCL13 (M2) were validated in human macrophages and applied to a global analysis of GBM tissue. Furthermore, proteinase genes, known to be associated with GBM progression (ADAM8, MMP9, MMP14, ADAM10, ADAM17), were analyzed in correlation to M1/M2 markers. Notably, expression levels of ADAM10 and ADAM17 are significantly correlated with an M1-like phenotype and are positively associated to patient survival. Whilst ADAM8 mRNA expression was equally correlated with M1- and M2-like markers, genes for MMP9 and MMP14 are significantly associated with an M2-like phenotype and association to impaired prognosis in the GBM patient cohort. Thus, we provide a robust and reliable combination of qPCR markers to characterize global microglia/macrophage status and the associated proteinase profiles in GBM patients that can be used to analyze the tumor microenvironment, the patients' prognosis and preselect those GBM patients for which targeting the microglia/macrophage population by repolarization might be beneficial.

journal_name

Biosci Rep

journal_title

Bioscience reports

authors

Gjorgjevski M,Hannen R,Carl B,Li Y,Landmann E,Buchholz M,Bartsch JW,Nimsky C

doi

10.1042/BSR20182361

subject

Has Abstract

pub_date

2019-06-20 00:00:00

issue

6

eissn

0144-8463

issn

1573-4935

pii

BSR20182361

journal_volume

39

pub_type

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