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IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13.
- Source :
-
Neoplasia (New York, N.Y.) [Neoplasia] 2002 Sep-Oct; Vol. 4 (5), pp. 388-99. - Publication Year :
- 2002
-
Abstract
- We have found that binding sites for interleukin-13 (IL-13) are overexpressed in a vast majority of high-grade astrocytomas (HGAs). These binding sites for IL-13 are distinct from the physiological receptor in that it does not bind IL-4. We also demonstrated that IL-13 receptor alpha 2 protein chain (IL-13Ralpha2), an IL-4-independent receptor for IL-13, is abundant among HGAs, but not in normal organs. To examine if IL-13Ralpha2 is the tumor-associated site for IL-13, we stably transfected normal Chinese hamster ovary (CHO) cells and glioma G-26 cells to express either human (h) or murine (m) IL-13Ralpha2. CHO-hIL-13Ralpha2(+) cells and G-26-h/mIL-13Ralpha2(+) cells, and not CHO and G-26 parental or mock-transfected cells, specifically bound IL-13 in an IL-4-independent manner. The IL-13Ralpha2(+) cells also became highly susceptible to the killing by an IL-13-based cytotoxic fusion protein. In loss of function studies, a HGA cell line, SNB-19, was transfected with antisense (as) hIL-13Ralpha2. as-SNB-19-hIL-13Ralpha2(+) cells lost their natural affinity towards IL-13 and became resistant to IL-13-based cytotoxins. The fact, that IL-13Ralpha2-positive cells bind IL-13 independent of IL-4, become susceptible to IL-13 cytotoxins, and cells deprived of IL-13Ralpha2 receptor lose these features, demonstrates that IL-13Ralpha2 is the brain tumor-associated receptor for IL-13.
- Subjects :
- Animals
Binding Sites
Blotting, Northern
Brain Neoplasms pathology
CHO Cells metabolism
Cricetinae
DNA Primers chemistry
DNA, Antisense pharmacology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Glioma pathology
Humans
Interleukin-13 Receptor alpha1 Subunit
Interleukin-4 metabolism
Polymerase Chain Reaction
Protein Binding
RNA metabolism
Receptors, Interleukin genetics
Receptors, Interleukin-13
Transfection
Tumor Cells, Cultured
Brain Neoplasms metabolism
Glioma metabolism
Interleukin-13 metabolism
Receptors, Interleukin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-8002
- Volume :
- 4
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neoplasia (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 12192597
- Full Text :
- https://doi.org/10.1038/sj.neo.7900234