title: Adenoviruses-mediated transduction of human oesophageal carcinoma cells with the interferon-λ genes produced anti-tumour effects.
abstract: BACKGROUND
  Interferon-λs (IFN-λs) are novel cytokines with multiple functions, like IFN-α and -β. We examined possible anti-tumour effects produced by adenoviruses bearing the IFN-λ1 or -λ2 gene (Ad/IFN-λ) with the type-35 fibre-knob structure.
  
  
  METHODS
  Proliferation of oesophageal carcinoma cells transduced with Ad/IFN-λ and mechanisms of the inhibited growth were investigated.
  
  
  RESULTS
  Transduction with Ad/IFN-λ upregulated the expression of the class I antigens of the major histocompatibility complexes and induced the growth suppression. Increased sub-G1 populations and the cleavage of caspase-3 and poly (ADP-ribose) polymerase were detected in IFN-λ-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-λ-infected YES-2 cells subsequently reduced the tumourigenicity. Adenovirus/IFN-λ-infected fibroblasts, negative for the IFN-λ 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-λ-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 CD31-positive cells.
  
  
  CONCLUSIONS
  Adenovirus/IFN-λ induced apoptosis, and fibroblast-mediated delivery of IFN-λs is a potential cancer treatment by inducing direct cell death of the target carcinoma.
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center, Chiba 260-8717, Japan.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Kawamura
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
authors.forename: H
authors.initials: H
authors.lastname: Fujie
authors.forename: M
authors.initials: M
authors.lastname: Numasaki
authors.forename: M
authors.initials: M
authors.lastname: Namba
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: H
authors.initials: H
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Tagawa
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda