Trace metals and cancer: The case of neuroblastoma

N-myc oncogene amplification is one of the most established prognostic fact ors in neuroblastoma (NB), a young children solid tumor. Amounts of ferriti n, an iron storage protein, are abnormally increased in serum of patients w ith advanced stage disease. N-myc amplified NB cells can synthesize zinc me talloenzymes allowing tumor invasion and metastases formation. The aim of t his study was to find a relationship between N-myc amplification and trace metals in human neuroblasts. Coupling PIXE and RBS techniques, nuclear micr oprobe allowed to analyze elemental distributions and to determine trace me tal concentrations within cultured neuroblasts characterized by various deg rees of N-myc amplification. They were compared to trace metal distribution s and concentrations in tumor xenograft models of human NB, after injection of cells from the same lines in athymic nude mice. Our data allowed to est ablish a relation between trace metal contents and mechanisms of NB oncogen esis, amplified cell lines representing more aggressive phenotypes of the d isease. They should be confirmed by analysis of cultured neuroblasts and tu mors issued from a nonamplified cell line transfected with the N-myc oncoge ne. (C) 2001 Elsevier Science B.V. All rights reserved.