Interferon-λ induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents

Quanhai Li, Kiyoko Kawamura, Guangyu Ma, Fumi Iwata, Muneo Numasaki, Nobuo Suzuki, Hideaki Shimada, Masatoshi Tagawa

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Signal pathways of novel type III interferons (IFN-λs) are similar to those of type I IFNs (IFN-α/β) but their distinct functions have not been well characterised. We examined the growth suppressive activity of IFN-λ1 with nine human oesophageal carcinoma cell lines expressing the IFN-λ receptor complexes. Among them, three lines but not others showed IFN-λ1-mediated growth suppression by inducing G1 phase arrest or apoptosis. The G1 phase arrest was accompanied by the up-regulation of p21 and dephosphorylation of retinoblastoma (Rb), and the apoptosis was evidenced by cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Similar but not identical susceptibility was found in IFN-α-treated oesophageal carcinoma cells. Despite the differential suppressive responses among the cells, all the cells increased the expression of the myxovirus resistance A (MxA) and 2′,5′-oligoadenylate synthetase (2′,5′-OAS) genes and class I antigens of the major histocompatibility complexes (MHC) with IFN-λ1 treatment. Fibroblasts and mesenchymal stem cells, positive for IFN-α receptor (IFNAR), lacked one of the IFN-λ receptor complexes and Het-1A, immortalised oesophageal epithelium cells, were insensible to the IFN-λ1-induced growth suppression. IFN-λ1 produced combinatory anti-tumour effects with chemotherapeutic agents, cisplatin (CDDP) and 5-fluorouracil (5-FU), in IFN-λ1-sensitive oesophageal carcinoma cells but not in normal or Het-1A cells, while IFN-α achieved the combinatory suppressive effects to normal cells. These data collectively show that IFN-λ1 responsiveness is tissue-specific due to the restricted receptors expression and is diversified even among cells of the same lineage, and suggest that IFN-λ1 is a potential therapeutic agent for oesophageal carcinoma without damaging surrounding tissues.

Original languageEnglish
Pages (from-to)180-190
Number of pages11
JournalEuropean Journal of Cancer
Volume46
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1
Externally publishedYes

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Chemotherapy
  • IFN-λ
  • Oesophageal carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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