Abstract
The interleukin-13 receptor alpha2 (IL-13Rα2) is a cancer-associated receptor overexpressed in human glioblastoma multiforme (GBM). This receptor is undetectable in normal brain which makes it a highly suitable target for diagnostic and therapeutic purposes. However, the pathological role of this receptor in GBM remains to be established. Here we report that IL-13Rα2 alone induces invasiveness of human GBM cells without affecting their proliferation. In contrast, in the presence of the mutant EGFR (EGFRvIII), IL-13Rα2 promotes GBM cell proliferation in vitro and in vivo. Mechanistically, the cytoplasmic domain of IL-13Rα2 specifically binds to EGFRvIII, and this binding upregulates the tyrosine kinase activity of EGFRvIII and activates the RAS/RAF/MEK/ERK and STAT3 pathways. Our findings support the “To Go or To Grow” hypothesis whereby IL-13Rα2 serves as a molecular switch from invasion to proliferation, and suggest that targeting both receptors with STAT3 signaling inhibitor might be a therapeutic approach for the treatment of GBM.
Highlights
The interleukin-13 receptor alpha[2] (IL-13Rα2) is a cancer-associated receptor overexpressed in human glioblastoma multiforme (GBM)
With the exception of one sample, all GBM samples expressed IL-13Rα2 to varying degree (~64-kDa and detectable levels of both wtEGFR (~170kDa) and mutant EGFRvIII (~145kDa) proteins (Fig. 1d), suggesting that these receptors may play a role in gliomagenesis
We revealed a critical role for IL-13Rα2 in GBM tumor cell migration and growth; it can serve as a modulator between cellular migration and proliferation, depending in part on its ability to engage with other tyrosine kinase receptors crosstalk activities, providing further support to the “To Go or Grow” theory during the progression of human gliomas (Fig. 7g)
Summary
The interleukin-13 receptor alpha[2] (IL-13Rα2) is a cancer-associated receptor overexpressed in human glioblastoma multiforme (GBM). Two commonly expressed tumor antigens in GBM include the epidermal growth factor receptor mutant (EGFRvIII) and the interleukin-13 receptor alpha 2 (IL-13Rα2), which are potential targets for the treatment of GBM2,3. Apart from high-grade gliomas, the receptor has been reported to be overexpressed in several types of human tumors, including head and neck cancer[22], kidney cancer[23], prostate cancer[24], ovarian cancer[25], adrenocortical carcinoma[26], clear cell renal cell carcinoma[27], and Kaposi’s sarcoma[28]. In the presence of the mutant EGFR (EGFRvIII), IL-13Rα2 interacts with EGFRvIII to promotes GBM growth through upregulation of EGFRvIII tyrosine kinase activities and subsequently the RAS/RAF/MEK/ERK and STAT3 pathways
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
