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Article

IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells

  • Authors:
    • Nihal Karakaş
    • Daniel Stuckey
    • Esther Revai‑Lechtich
    • Khalid Shah
  • View Affiliations / Copyright

    Affiliations: Center for Stem Cell Therapeutics and Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Article Number: 145
    |
    Published online on: June 3, 2021
       https://doi.org/10.3892/ijmm.2021.4978
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Abstract

Glioblastomas (GBMs) are refractory to current treatments and novel therapeutic approaches need to be explored. Pro‑apoptotic tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is tumor‑specific and has been shown to induce apoptosis and subsequently kill GBM cells. However, approximately 50% of GBM cells are resistant to TRAIL and a combination of TRAIL with other therapeutics is necessary to induce mechanism‑based cell death in TRAIL‑resistant GBMs. The present study examined the ability of the tumor cell surface receptor, interleukin (IL)‑13 receptor α2 (IL13Rα2)‑ and epidermal growth factor receptor (EGFR)‑targeted pseudomonas exotoxin (PE) to sensitize TRAIL‑resistant GBM cells and assessed the dual effects of interleukin 13‑PE (IL13‑PE) or EGFR nanobody‑PE (ENb‑PE) and TRAIL for the treatment of a broad range of brain tumors with a distinct TRAIL therapeutic response. Receptor targeted toxins upregulated TRAIL death receptors (DR4 and DR5) and suppressed the expression of anti‑apoptotic FLICE‑inhibitory protein (FLIP) and X‑linked inhibitor of apoptosis protein (XIAP). This also led to the induction of the cleavage of caspase‑8 and caspase‑9 and resulted in the sensitization of highly resistant established GBM and patient‑derived GBM stem cell (GSC) lines to TRAIL‑mediated apoptosis. These findings provide a mechanism‑based strategy that may provide options for the cell‑mediated delivery of bi‑functional therapeutics to target a wide spectrum of TRAIL‑resistant GBMs.
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Copy and paste a formatted citation
Spandidos Publications style
Karakaş N, Stuckey D, Revai‑Lechtich E and Shah K: IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells. Int J Mol Med 48: 145, 2021.
APA
Karakaş, N., Stuckey, D., Revai‑Lechtich, E., & Shah, K. (2021). IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells. International Journal of Molecular Medicine, 48, 145. https://doi.org/10.3892/ijmm.2021.4978
MLA
Karakaş, N., Stuckey, D., Revai‑Lechtich, E., Shah, K."IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells". International Journal of Molecular Medicine 48.1 (2021): 145.
Chicago
Karakaş, N., Stuckey, D., Revai‑Lechtich, E., Shah, K."IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells". International Journal of Molecular Medicine 48, no. 1 (2021): 145. https://doi.org/10.3892/ijmm.2021.4978
Copy and paste a formatted citation
x
Spandidos Publications style
Karakaş N, Stuckey D, Revai‑Lechtich E and Shah K: IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells. Int J Mol Med 48: 145, 2021.
APA
Karakaş, N., Stuckey, D., Revai‑Lechtich, E., & Shah, K. (2021). IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells. International Journal of Molecular Medicine, 48, 145. https://doi.org/10.3892/ijmm.2021.4978
MLA
Karakaş, N., Stuckey, D., Revai‑Lechtich, E., Shah, K."IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells". International Journal of Molecular Medicine 48.1 (2021): 145.
Chicago
Karakaş, N., Stuckey, D., Revai‑Lechtich, E., Shah, K."IL13Rα2‑ and EGFR‑targeted pseudomonas exotoxin potentiates the TRAIL‑mediated death of GBM cells". International Journal of Molecular Medicine 48, no. 1 (2021): 145. https://doi.org/10.3892/ijmm.2021.4978
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