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

• Published in: British journal of cancer 2004-06, Vol.90 (11), p.2210-2218
• Main Authors: Airoldi, I, Meazza, R, Croce, M, Di Carlo, E, Piazza, T, Cocco, C, D'Antuono, T, Pistoia, V, Ferrini, S, Corrias, M V
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Division - drug effects; DNA Primers; Drug Resistance; Epidemiology; Female; Flow Cytometry; Genetic Therapy; Humans; Interferon-gamma - biosynthesis; Interferon-gamma - pharmacology; Medical sciences; Mice; Mice, Nude; Molecular and Cellular Pathology; Molecular Medicine; Neoplasms, Experimental; Neovascularization, Pathologic; Neuroblastoma - immunology; Neuroblastoma - pathology; Neurology; Oncology; Phenotype; Receptors, Tumor Necrosis Factor - analysis; Reverse Transcriptase Polymerase Chain Reaction; Transfection; Tumor Cells, Cultured; Tumors of the nervous system. Phacomatoses
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6601842

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.