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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Expression and structure of interleukin 4 receptors in primary meningeal tumors
Sachin Puri1, Bharat H Joshi, Chitra Sarkar
1Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Background:
It was reported previously that malignant human tumors, like glioma and medulloblastoma, express high-density interleukin (IL-4) receptor mRNA and protein. Because IL-4 receptors (R) are sensitive targets for targeted therapeutics, knowledge of the expression of these receptors in other central nervous system tumors is of great interest. In this study, the authors examined the expression and subunit composition of IL-4R complex in primary human meningiomas.
Methods:
Reverse transcription-polymerase chain reaction (RT-PCR) analysis for IL-13Ralpha1, IL-4Ralpha and IL-2Rgammac was performed on total RNA extracted from 35 meningiomas and a normal human brain tissue sample. Results were confirmed in nine randomly selected tumors by quantitative real-time PCR and in situ immunofluorescence assay.
Results:
Transcripts for the IL-4Ralpha and IL-13Ralpha1 chains were overexpressed in meningiomas compared with normal brain tissue. The levels of IL-4Ralpha mRNA appeared to be higher compared with the levels of IL-13Ralpha1 mRNA. The results also showed that tumors with higher disease grade tended to have increased mRNA expression for the IL-4Ralpha chain. This IL-4Ralpha mRNA overexpression appeared to be more frequent in younger patients (age < 37 years). The transcripts for IL-2Rgammac chain were not detected in any of the tumor samples or in normal brain tissue. Quantitative real-time PCR confirmed the results of the RT-PCR analysis. Meningiomas also demonstrated a bright immunofluorescent staining for the IL-4Ralpha and IL-13Ralpha1 chains but no staining for IL-2Rgammac.
Conclusions:
Expression of the IL-4Ralpha and IL-13Ralpha1 chains and absence of IL-2gammac expression established that meningiomas expressed type II IL-4Rs. These receptors may serve as a target for cytotoxin/immunotoxin therapy in patients with meningioma who are not amenable to surgical resection or for recurrent tumors.
Insights
Meningiomas express type II interleukin-4 receptors (IL-4Rs), specifically IL-4Ralpha and IL-13Ralpha1 chains. These receptors present a potential therapeutic target for meningioma treatment, especially for recurrent or unresectable tumors.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Malignant brain tumors like glioma and medulloblastoma exhibit high expression of interleukin-4 receptor (IL-4R) mRNA and protein.
- IL-4Rs are recognized as sensitive targets for targeted therapeutic strategies.
- Investigating IL-4R expression in other central nervous system tumors, such as meningiomas, is of significant clinical interest.
Purpose of the Study:
- To investigate the expression and subunit composition of the IL-4R complex in primary human meningiomas.
- To determine if meningiomas express IL-4R chains relevant for targeted therapies.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze IL-13Ralpha1, IL-4Ralpha, and IL-2Rgammac transcripts in 35 meningiomas and normal brain tissue.
- Quantitative real-time PCR and in situ immunofluorescence assays were employed to validate RT-PCR findings in a subset of tumors.
Main Results:
- Meningiomas demonstrated overexpression of IL-4Ralpha and IL-13Ralpha1 mRNA compared to normal brain tissue.
- Higher expression of IL-4Ralpha mRNA correlated with increased tumor grade and was more frequent in younger patients (<37 years).
- IL-2Rgammac transcripts were not detected in meningiomas or normal brain tissue, while immunofluorescence confirmed IL-4Ralpha and IL-13Ralpha1 expression.
Conclusions:
- Meningiomas express type II IL-4Rs, characterized by the presence of IL-4Ralpha and IL-13Ralpha1 chains and the absence of IL-2Rgammac.
- These type II IL-4Rs represent a potential therapeutic target for cytotoxin or immunotoxin therapy in patients with meningioma.
- This finding is particularly relevant for meningioma cases that are not surgically resectable or for recurrent disease.
