Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells

Yasuhiro Tezuka, Shunsuke Endo, Aya Matsui, Atsuko Sato, Katsuyo Saito, Kentaro Semba, Masafumi Takahashi, Takashi Murakami

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24 Citations (Scopus)

Abstract

Interferon (IFN)-λs (IL-28A/IL-28B/IL-29) classified as type III IFNs, are the latest members identified of the interferon family. As with type I IFNs such as IFN-α, type III IFNs share antiviral and antitumor activity and may have fewer side effects due to a more selective receptor distribution. Therefore, type III IFNs may be clinically useful for human viral and malignant diseases. Here we demonstrate the potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells. All lung cancer cell lines that we examined expressed both IFN-λ receptors (IL-28R1 and IL-10R2). Lung cancer cells with epidermal growth factor receptor (EGFR) mutations were more sensitive to IFN-λ2 treatment compared with cells with KRAS mutations. HCC827 cells with an EGFR mutation treated with IFN-λ2 underwent growth suppression and apoptotic cell death by STAT1 phosphorylation. Administration of neutralizing antibodies to IFN-λ inhibited caspase-3/7 activity induced by IFN-λ2. Finally, in vivo luminescent imaging also demonstrated the anti-tumor effect of IFN-λ2 in a cancer cell transplant animal model. Taken together, IFN-λ2 would be a new therapeutic agent for clinical lung cancers with EGFR mutations.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalLung Cancer
Volume78
Issue number3
DOIs
Publication statusPublished - 2012 Dec 1

Keywords

  • Apoptosis
  • Bioluminescent imaging
  • EGFR mutation
  • IL-28A
  • Non-small cell lung cancer
  • Type III interferon

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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  • Cite this

    Tezuka, Y., Endo, S., Matsui, A., Sato, A., Saito, K., Semba, K., Takahashi, M., & Murakami, T. (2012). Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells. Lung Cancer, 78(3), 185-192. https://doi.org/10.1016/j.lungcan.2012.09.005