Novel peptides secreted from human neuroblastoma: useful clinical tools?

Abstract

Background Differentially expressed neuroblastoma (NB) proteins are vital for the development of new diagnostics and therapeutics. For example, secretory NB peptides (neuron-specific enolase and chromogranins) are clinically useful. We investigated polypeptide secretion by employing proteomic technologies to analyze proteins released from cultured NB cells. Methods Neuroblastoma cell lines (SK-N-AS, SK-N-DZ, and SK-N-FI) were grown in serum-free media. Conditioned media from each cell line was analyzed for secreted proteins by 2-dimensional polyacrylamide gel electrophoresis. Selected polypeptides were identified by liquid chromatography–linked tandem mass spectrometry. Results We identified 5 polypeptides that were secreted or shed by NB. Ubiquitin, β 2-microglobulin, insulin-like growth factor binding protein–2, superoxide dismutase (copper and zinc), and heat shock cognate 70-kd proteins were secreted from NB cells, as compared with control media. Elevated levels of these proteins have been described in serum/tissues under intracellular stress and malignancies, including NB. Conclusion These novel secretory polypeptides may contribute to NB growth. The proteins may reveal additional tumor markers and permit putative use in the diagnosis and treatment of NB. Detection of these proteins in serum of children with NB vs controls (using 2-dimensional polyacrylamide gel electrophoresis and mass spectrometry techniques) is currently in progress.