Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas.
Glioblastoma multiforme (GBM) is an incurable brain tumor. Due to the striking heterogeneity that characterizes GBM, there is no known tumor-specific antigen or receptor that is expressed by a majority of GBM patients. We found that virtually all studied human GBM specimens (23 samples) abundantly expressed a receptor for interleukin (IL)-13 in situ, whereas normal human brain had few, if any, IL-13-binding sites. The GBM-associated IL-13 receptor was both quantitatively and qualitatively different from and, thus, more restrictive than the shared signaling receptor of normal tissue: it was IL-4 independent. The receptor for IL-13 was overexpressed by a majority of cancer cells in situ. Furthermore, cytotoxins targeted to this more restrictive IL-13R produced cures in animals bearing xenografts of human high-grade gliomas. Thus, unexpectedly, the receptor for an immune regulatory cytokine may be a long sought marker and, concomitantly, a unique imaging site and therapeutic target for GBM, the most malignant and the most heterogeneous of brain tumors.
Debinski
W
W
Department of Surgery, Pennsylvania State University College of Medicine, Hershey 17033-0850, USA. wdebinski@psghs.edu
Gibo
D M
DM
Hulet
S W
SW
Connor
J R
JR
Gillespie
G Y
GY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D018793:Interleukin-13 / Q000378:metabolism; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000032:analysis*; D018123:Receptors, Interleukin / Q000032:analysis*; D053660:Receptors, Interleukin-13; D011994:Recombinant Proteins / Q000378:metabolism; D014183:Transplantation, Heterologous
D014408:Biomarkers, Tumor; C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D000922:Immunotoxins; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D011994:Recombinant Proteins; D015847:Interleukin-4