Scientific Publications by FDA Staff
Cancer 2005 May 15;103(10):2132-42
Expression and structure of interleukin 4 receptors in primary meningeal tumors.
Puri S, Joshi BH, Sarkar C, Mahapatra AK, Hussain E, Sinha S
Sinha S, All India Inst Med Sci, Dept Biochem, New Delhi 110029, India All India Inst Med Sci, Dept Biochem, New Delhi 110029, India Jamia Millia Islamia, Dept Biosci, New Delhi 110025, India US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA All India Inst Med Sci, Dept Pathol, New Delhi 110029, India All India Inst Med Sci, Dept Neurosurg, 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. Cancer 2005. (c) 2005 American Cancer Society.
|Category: Journal Article|
|PubMed ID: #15830341|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|