Type III interferon induces apoptosis in human lung cancer cells

Li,Wei; Huang,Xiaojie; Liu,Zhuoming; Wang,Yuxuan; Zhang,Hongwei; Tong,Hongfei; Wu,Hao; Lin,Shengzhang

doi:10.3892/or.2012.1901

Type III interferon induces apoptosis in human lung cancer cells

Authors:
- Wei Li
- Xiaojie Huang
- Zhuoming Liu
- Yuxuan Wang
- Hongwei Zhang
- Hongfei Tong
- Hao Wu
- Shengzhang Lin
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Affiliations: Department of Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, P.R. China, Case Comprehensive Cancer Center and Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA, Materials Science and Engineering Program, State University of New York at Binghamton, Binghamton, NY 13902, USA, Department of General Surgery, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325027, P.R. China
Published online on: July 5, 2012 https://doi.org/10.3892/or.2012.1901
Pages: 1117-1125

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Abstract

The apoptotic effects of interferon lambdas (IFNλs) have been described in several types of cancers. However, their effects on human lung cancer cells and the mechanisms are elusive. In addition, the interaction between IFNλs and other interferons remains unclear. The interplay between IFNα and IFNλ has been reported. However, although IFNγ is a well-known regulatory interferon, the mechanisms through which it regulates IFNλs in lung cancer cells are unknown. These issues are critical for the application of IFNλs in lung cancer therapy. In this study, we used A549, a cell line derived from a human lung carcinoma, to characterize the antiproliferative and apoptotic effects of IFNλs on lung cancer, and the interplay between IFNγ and IFNλ. Because overexpression of full-length ectopic IFNλR1 led to cell death, we generated A549 cells stably expressing a chimeric receptor (10R1/λR1), which is composed of the extracellular domain of IL-10 receptor (IL10R1) fused in tandem to the transmembrane and intracellular domains of the IFNλ receptor (IFNλR1). By comparing with A549 cells stably expressing its cognate vector, we demonstrated that IL-10 stimulation triggered the intracellular IFNλ signaling via 10R1/λR1 receptor. By using A549 cells expressing 10R1/λR1, we report that the IFNλR1 chain of IFNλ receptor possesses an intrinsic ability to trigger apoptosis in human lung cancer cells. Although it did not suppress cell proliferation, IFNλ signaling via 10R1/λR1 receptor induced cell cycle arrest, externalization of phosphatidylserine, DNA fragmentation, activation of caspase-3, caspase-8 and caspase-9. However, the caspase inhibitor Z-VAD-FMK did not prevent apoptosis. In addition, the extent of induced apoptosis correlate with the expression levels of the IFNλ receptor and the levels of STAT1 activation. Lastly, we demonstrated that IFNγ sensitized A549 cells to IFNλ-induced apoptosis, via upregulation of IFNλR1. These data indicate the potential of IFNλ, alone or in combination with IFNγ, in the treatment of human lung carcinoma.

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