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 Senba, Masafumi Takahashi, Takashi Murakami

    Research output: Contribution to journalArticle

    22 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

    Fingerprint

    Interferons
    Interleukin-2
    Lung Neoplasms
    Neoplasms
    Epidermal Growth Factor Receptor
    Mutation
    Interferon Receptors
    Caspase 7
    Virus Diseases
    Neutralizing Antibodies
    Caspase 3
    Antiviral Agents
    Cell Death
    Animal Models
    Phosphorylation
    Transplants
    Cell Line
    Growth

    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

    Cite this

    Tezuka, Y., Endo, S., Matsui, A., Sato, A., Saito, K., Senba, K., ... 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

    Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells. / Tezuka, Yasuhiro; Endo, Shunsuke; Matsui, Aya; Sato, Atsuko; Saito, Katsuyo; Senba, Kentaro; Takahashi, Masafumi; Murakami, Takashi.

    In: Lung Cancer, Vol. 78, No. 3, 12.2012, p. 185-192.

    Research output: Contribution to journalArticle

    Tezuka, Y, Endo, S, Matsui, A, Sato, A, Saito, K, Senba, K, Takahashi, M & Murakami, T 2012, 'Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells', Lung Cancer, vol. 78, no. 3, pp. 185-192. https://doi.org/10.1016/j.lungcan.2012.09.005
    Tezuka, Yasuhiro ; Endo, Shunsuke ; Matsui, Aya ; Sato, Atsuko ; Saito, Katsuyo ; Senba, Kentaro ; Takahashi, Masafumi ; Murakami, Takashi. / Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells. In: Lung Cancer. 2012 ; Vol. 78, No. 3. pp. 185-192.
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