Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and pseudomonas exotoxin.
Recently, we have demonstrated that a spectrum of human adenocarcinoma cell lines express binding sites for interleukin 13 (IL-13). These cells are killed by a chimeric protein composed of human (h) IL-13 and a derivative of Pseudomonas exotoxin, PE38QQR (Debinski et al., J. Biol. Chem., 270: 16775-16780, 1995). The cell killing was hIL-13- and hIL-4-specific, indicating that a common binding site for the two cytokines is present in several solid tumor cell lines. Herein, we report that an array of established glioma cell lines is killed by very low concentrations of hIL-13-PE38QQR, often reaching <1 ng/ml (<20 pM). Glioma cells express up to 30,000 molecules of IL-13 receptor/cell which has intermediate affinity toward hIL-13. hIL-13-PE38QQR is more active (up to 3 logs difference in cytotoxic activities) than are the corresponding chimeric toxins containing hIL-4 or hIL-6. The cytotoxic action of hIL-13-PE38QQR is blocked by an excess of hIL-13 on all cell lines studied, and it is not neutralized by hIL-4 on some of these cells. Our results show that human brain cancers richly express receptors for IL-13. Furthermore, the interaction detected previously between receptors for IL-13 and IL-4 on solid tumors cell lines is of a qualitatively different character in U-251 MG and U-373 MG glioma cells. The receptor for IL-13 may represent a new marker of brain cancers and an attractive target for anticancer therapies.
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The Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Department of Surgery, Division of Neurosurgery, Hershey, Pennsylvania 17033, USA. debinski@debin.nsr.hmc.psu.edu
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D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D004354:Drug Screening Assays, Antitumor; D005098:Exotoxins / Q000627:therapeutic use*; D005910:Glioma / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D018793:Interleukin-13 / Q000627:therapeutic use*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D014407:Tumor Cells, Cultured / Q000187:drug effects; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4; D009363:Neoplasm Proteins; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C508181:IL13RA1 protein, human