IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13.
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.
Mintz
Akiva
A
Section of Neurosurgery/H110, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033-0850, USA.
Gibo
Denise M
DM
Slagle-Webb
Becky
B
Christensen
Neil D
ND
Debinski
Waldemar
W
D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D017931:DNA Primers / Q000737:chemistry; D016373:DNA, Antisense / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016373:DNA, Antisense; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4; D012313:RNA