Dataset Information

Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.

ABSTRACT: Objective. Some effects of progesterone on glioma cells can be explained through the slow, genomic mediated response via nuclear receptors; the other effects suggest potential role of a fast, nongenomic action mediated by membrane-associated progesterone receptors. Methods. The effects of progesterone treatment on the expression levels of progesterone receptor membrane component 1 (PGRMC1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1), and progestin and adipoQ receptor 7 (PAQR7) on both mRNA and protein levels were investigated in spheroids derived from human glioma cell lines U-87 MG and LN-229. Results. The only significant alteration at the transcript level was the decrease in PGRMC1 mRNA observed in LN-229 spheroids treated with 30?ng/mL of progesterone. No visible alterations at the protein levels were observed using immunohistochemical analysis. Stimulation of U-87 MG spheroids resulted in an increase of PGRMC1 but a decrease of PAIRBP1 protein. Double immunofluorescent detection of PGRMC1 and PAIRBP1 identified the two proteins to be partially colocalized in the cells. Western blot analysis revealed the expected bands for PGRMC1 and PAIRBP1, whereas two bands were detected for PAQR7. Conclusion. The progesterone action is supposed to be mediated via membrane-associated progesterone receptors as the nuclear progesterone receptor was absent in tested spheroids.

SUBMITTER: Hlavaty J

PROVIDER: S-EPMC4908248 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.

Hlavaty Juraj J Ertl Reinhard R Miller Ingrid I Gabriel Cordula C

BioMed research international 20160601

Objective. Some effects of progesterone on glioma cells can be explained through the slow, genomic mediated response via nuclear receptors; the other effects suggest potential role of a fast, nongenomic action mediated by membrane-associated progesterone receptors. Methods. The effects of progesterone treatment on the expression levels of progesterone receptor membrane component 1 (PGRMC1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1), and progestin and adipoQ receptor 7 (PAQR ...[more]

PMID: 27340667

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Project description:BackgroundClinical outcomes of patients with glioma are still poor, even after standard treatments, including surgery combined with radiotherapy and chemotherapy. New therapeutic strategies and targets for glioma are urgently needed. Plasminogen activator urokinase receptor (PLAUR), a highly glycosylated integral membrane protein, is reported to modulate plasminogen activation and extracellular matrix degradation in many malignant cancers, but its role in gliomas remains unclear.MethodsGlioma samples with mRNA sequencing data and clinical information from the Chinese Glioma Genome Atlas (n = 310) data set and The Cancer Genome Atlas (n = 611) data set were collected for this study. Analyses using Kaplan-Meier plots, time-dependent receiver operating characteristic curves, Cox regression, and nomograms were conducted to evaluate the prognostic performance of PLAUR expression. Analyses using Metascape, ESTIMATE, EPIC, and immunohistochemical staining were performed to reveal the potential biological mechanism. The statistical analysis and graphical work were completed using SPSS, R language, and GraphPad Prism.ResultsPLAUR was highly expressed in phenotypes associated with glioma malignancy and could serve as an independent prognostic indicator. Functional analysis revealed the correlation between PLAUR and immune response. Further studies found that samples with higher PLAUR expression were infiltrated with fewer CD8 T cells and many more M2 macrophages. Strong positive correlation was demonstrated between PLAUR expression and some immunosuppressive markers, including immune checkpoints and cytokines. These findings were also confirmed in patient samples.ConclusionOur results elucidated the clinical significance and immunosuppressive effect of PLAUR in gliomas, which might provide some clues in glioma immunotherapy.Implications for practiceAlthough the efficacy of immunotherapy has been verified in other tumors, its application in glioma is impeded because of the unique microenvironment. Tumor-associated macrophages, which are particularly abundant in a glioma mass, contribute much to the immunosuppressive microenvironment and offer new opportunities in glioma immunotherapy. The results of this study identified plasminogen activator urokinase receptor (PLAUR) expression as a potential marker to predict the infiltration of macrophages and the status of immune microenvironment in patients with glioma, suggesting that treatment decisions could be based on PLAUR level when administering immunotherapeutics. The soluble PLAUR in blood and other body fluids would make this approach easy to implement in the clinic.

Dataset Information

Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.

Publications

Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.

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