Adenoviruses-mediated transduction of human oesophageal carcinoma cells with the interferon-λ genes produced anti-tumour effects

BACKGROUND: Interferon-lambda s (IFN-lambda s) are novel cytokines with multiple functions, like IFN-alpha and -beta. We examined possible anti-tumour effects produced by adenoviruses bearing the IFN-lambda 1 or -lambda 2 gene (Ad/IFN-lambda) with the type-35 fibre-knob structure. METHODS: Proliferation of oesophageal carcinoma cells transduced with Ad/IFN-lambda and mechanisms of the inhibited growth were investigated. RESULTS: Transduction with Ad/IFN-lambda upregulated the expression of the class I antigens of the major histocompatibility complexes and induced the growth suppression. Increased sub-GI populations and the cleavage of caspase-3 and poly (ADP-ribose) polymerase were detected in IFN-lambda-sensitive YES-2 and T.Tn cells. The cell death was accompanied by cytoplasmic cytochrome C and increased cleaved caspase-9 and Bax expression, suggesting mitochondria-mediated apoptosis. Adenovirus/IFN-lambda-infected YES-2 cells subsequently reduced the tumourigenicity. Adenovirus/IFN-lambda-infected fibroblasts, negative for the IFN-lambda receptors, induced death of YES-2 or T.Tn cells that were co-cultured. Inoculation of YES-2 cells in nude mice, when mixed with the Ad/IFN-lambda-infected fibroblasts, resulted in retardation of the tumour growth. The growth suppression was not linked with upregulated CD69 expression on natural killer cells or increased numbers of CD3I-positive cells. CONCLUSION: Adenovirus/IFN-lambda induced apoptosis, and fibroblast-mediated delivery of IFN-lambda s is a potential cancer treatment by inducing direct cell death of the target carcinoma. British Journal of Cancer (2011) 105, 1302-1312. doi:10.1038/bjc.2011.379 www.bjcancer.com Published online 27 September 2011 (C) 2011 Cancer Research UK