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

Waldemar Debinski, Denise M. Gibo

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) IL13R alpha', a component of the signaling, heterodimeric high-affinity receptor for IL13 that is shared with IL4, and (2) IL13R alpha, a monomeric, IL4-independent receptor. We analyzed gene expression of IL13R alpha, IL13R alpha' and that of IL4Rbeta, which is the other subunit of the shared IL13/4 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. The most striking feature of the IL13R alpha gene expression was the virtual lack of its transcripts within the CNS. Furthermore, only the testes exhibited a prominent presence of the mRNA for IL13R alpha among peripheral organs. In contrast, the components of the shared IL13/4 receptor were readily detected both in the CNS and in vital organs, such as liver, heart, lungs, and gastrointestinal tract. 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 IL13R alpha resides on chromosome X. Since IL13R alpha is (1) a cancer-associated protein, (2) virtually restricted to testes among normal tissues, and (3) its gene is on chromosome X, IL13R alpha is unexpectedly categorized as a cancer/testis antigen. Our findings make IL13R alpha even more attractive as a target for variety of approaches in glioma molecular management.