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

Abstract

Background: The 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 Methods: We 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. Results: The 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. Conclusions: The 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.