Low-dose interferon-γ-producing human neuroblastoma cells show reduced proliferation and delayed tumorigenicity

I. Airoldi, R. Meazza, M. Croce, E. Di Carlo, T. Piazza, C. Cocco, T. D'Antuono, V. Pistoia, S. Ferrini, M. V. Corrias

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon-γ (IFN-γ) directs T helper-1 cell differentiation and mediates antitumour effects in preclinical models. However, high-dose IFN-γ is toxic in vivo, and IFN-γ-transfected neuroblastoma (NB) cells secreting high amounts of the cytokine may be lost due to cell apoptosis or differentiation. Two human NB cell lines (ACN and SK-N-BE2(c)) differing as to genetic and phenotypic features were transfected with the human IFN-γ gene and selected on the grounds of the low concentrations of IFN-γ produced. In both IFN-γ-transfected cell lines, autocrine and paracrine activation of IFN-γ-mediated pathways occurred, leading to markedly reduced proliferation rate, to increased expression of surface HLA and CD40 molecules and of functional TNF binding sites. ACN/IFN-γ cells showed a significantly delayed tumorigenicity in nude mice as compared to parental cells. ACN/IFN-γ tumours were smaller, with extensive necrotic area as a result of a damaged and defective microvascular network. In addition, a significant reduction in the proliferation index was observed. This is the first demonstration that IFN-γ inhibits in vivo proliferation of NB cell by acting on the tumour cell itself. This effect adds to the immunoregulatory and antiangiogenic activities operated by IFN-γ in syngeneic tumour-bearing hosts.

Original languageEnglish
Pages (from-to)2210-2218
Number of pages9
JournalBritish Journal of Cancer
Volume90
Issue number11
Publication statusPublished - Jun 1 2004

Keywords

  • Cancer vaccine
  • IFN-γ
  • Neuroblastoma
  • Transfection
  • Tumour gene therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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