TY - JOUR
T1 - IL-13Rα2 is a glioma-restricted receptor for interleukin-13
AU - Mintz, Akiva
AU - Gibo, Denise M.
AU - Slagle-Webb, Becky
AU - Christensen, Neil D.
AU - Debinski, Waldemar
N1 - Funding Information:
Abbreviations: as, antisense; CHO cells, Chinese hamster ovary cells; CTA, cancer/ testis antigen; IH, immunohistochemistry; h, human; HGA, high-grade astrocytoma; IL-4, interleukin -4; IL - 13, interleukin-13; m, murine; PE, Pseudomonas exotoxin Address all correspondence to: Dr. Waldemar Debinski, Section of Neurosurgery/H110, Department of Surgery, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 - 0850, USA. E - mail: wdebinski@psu.edu 1This work was supported by the National Institutes of Health grant R01 CA74145. Received 10 December 2001; Accepted 27 December 2001.
PY - 2002
Y1 - 2002
N2 - 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-13Rα2), an IL-4-independent receptor for IL-13, is abundant among HGAs, but not in normal organs. To examine if IL-13Rα2 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-13Rα2. CHO-hIL-13Rα2(+) cells and G-26-h/mIL-13Rα2(+) cells, and not CHO and G-26 parental or mock-transfected cells, specifically bound IL-13 in an IL-4-independent manner. The IL-13Rα2(+) 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-13Rα2. as-SNB-19-hIL-13Rα2(+) cells lost their natural affinity towards IL-13 and became resistant to IL-13-based cytotoxins. The fact, that IL-13Rα2-positive cells bind IL-13 independent of IL-4, become susceptible to IL-13 cytotoxins, and cells deprived of IL-13Rα2 receptor lose these features, demonstrates that IL-13Rα2 is the brain tumor-associated receptor for IL-13.
AB - 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-13Rα2), an IL-4-independent receptor for IL-13, is abundant among HGAs, but not in normal organs. To examine if IL-13Rα2 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-13Rα2. CHO-hIL-13Rα2(+) cells and G-26-h/mIL-13Rα2(+) cells, and not CHO and G-26 parental or mock-transfected cells, specifically bound IL-13 in an IL-4-independent manner. The IL-13Rα2(+) 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-13Rα2. as-SNB-19-hIL-13Rα2(+) cells lost their natural affinity towards IL-13 and became resistant to IL-13-based cytotoxins. The fact, that IL-13Rα2-positive cells bind IL-13 independent of IL-4, become susceptible to IL-13 cytotoxins, and cells deprived of IL-13Rα2 receptor lose these features, demonstrates that IL-13Rα2 is the brain tumor-associated receptor for IL-13.
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U2 - 10.1038/sj.neo.7900234
DO - 10.1038/sj.neo.7900234
M3 - Article
C2 - 12192597
AN - SCOPUS:0036708502
VL - 4
SP - 388
EP - 399
JO - Neoplasia
JF - Neoplasia
SN - 1522-8002
IS - 5
ER -