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BackgroundThe vast majority of patients with high-grade gliomas (HGG) over-express interleukin 4 (IL4)-independent binding sites for IL13 in situ. In addition, mutated IL13-based cytotoxins directed specifically toward glioma-associated sites are arguably the most active anti-glioma agents. Two IL13 receptor (R) proteins were identified: (1) IL13Ra′, a component of the signaling, het-erodimeric high-affinity receptor for IL13 that is shared with IL4, and (2) IL13Rα, a monomeric, IL4-independent receptor.Materials and MethodsWe analyzed gene expression of IL13Rα, IL13Rα′ and that of IL4Rβ, which is the other subunit of the shared ILl3/4 receptor. The study was conducted with 40 human normal adult tissues, 20 discrete regions of the central nervous system (CNS), 7 fetal tissues, several cultured cell lines, and surgical CNS specimens.ResultsThe most striking feature of the IL13Rα gene expression was the virtual lack of its transcripts within the CNS. Furthermore, only the testes exhibited a prominent presence of the mRNA for IL13Rα among peripheral organs. In contrast, the components of the shared ILl3/4 receptor were readily detected both in the CNS and in vital organs, such as liver, heart, lungs, and gastrointestinal tract.ConclusionsThe results strongly support a need to redirect IL13 towards its more restrictive, IL4-independent, receptor for glioma diagnosis and therapies. Moreover, the gene for IL13Rα resides on chromosome X. Since IL13Rα is (1) a cancer-associated protein, (2) virtually restricted to testes among normal tissues, and (3) its gene is on chromosome X, IL13Rα is unexpectedly categorized as a cancer/testis antigen. Our findings make IL13Rα even more attractive as a target for variety of approaches in glioma molecular management.

Molecular Expression Analysis of Restrictive Receptor for Interleukin 13, a Brain Tumor-associated Cancer/Testis Antigen