Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adolescent
-
Adult
-
Aged
-
Animals
-
Biomarkers, Tumor / analysis*
-
Brain Chemistry
-
Brain Neoplasms / chemistry*
-
Brain Neoplasms / genetics
-
Brain Neoplasms / pathology
-
Brain Neoplasms / therapy
-
Female
-
Gene Expression Regulation, Neoplastic
-
Glioblastoma / chemistry*
-
Glioblastoma / genetics
-
Glioblastoma / pathology
-
Glioblastoma / therapy
-
Humans
-
Immunotoxins / therapeutic use
-
Interleukin-13 / metabolism
-
Interleukin-13 Receptor alpha1 Subunit
-
Interleukin-4 / pharmacology
-
Male
-
Mice
-
Mice, Nude
-
Mice, SCID
-
Middle Aged
-
Neoplasm Proteins / analysis*
-
Neoplasm Transplantation
-
Nerve Tissue Proteins / analysis*
-
Receptors, Interleukin / analysis*
-
Receptors, Interleukin-13
-
Recombinant Proteins / metabolism
-
Transplantation, Heterologous
Substances
-
Biomarkers, Tumor
-
IL13RA1 protein, human
-
Il13ra1 protein, mouse
-
Immunotoxins
-
Interleukin-13
-
Interleukin-13 Receptor alpha1 Subunit
-
Neoplasm Proteins
-
Nerve Tissue Proteins
-
Receptors, Interleukin
-
Receptors, Interleukin-13
-
Recombinant Proteins
-
Interleukin-4