Expression and structure of interleukin 4 receptors in primary meningeal tumors.
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.
Puri
Sachin
S
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Joshi
Bharat H
BH
Sarkar
Chitra
C
Mahapatra
Ashok Kumar
AK
Hussain
Ejaz
E
Sinha
Subrata
S
D000328:Adult; D000367:Age Factors; D001923:Brain Chemistry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit; D018793:Interleukin-13 / Q000737:chemistry; D053661:Interleukin-13 Receptor alpha1 Subunit; D008577:Meningeal Neoplasms / Q000737:chemistry* / Q000235:genetics; D008579:Meningioma / Q000737:chemistry* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000737:chemistry; D053660:Receptors, Interleukin-13; D015375:Receptors, Interleukin-2 / Q000737:chemistry; D019948:Receptors, Interleukin-4 / Q000737:chemistry* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C508181:IL13RA1 protein, human; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4