Discovery of new therapeutic targets in Neuroblastoma by means of proteomic approach and functional studies

摘要: Neuroblatoma (NB) is an embryonal tumor of the sympathetic nervous system which arises from neural crest cells. This disease rappresents most common extracranial in infants, accounting for 8% to 10% all childhood cancer and approximately 15% deaths children. NB a heterogeneous biology dictates clinical behaviour. It comprises cases with divergent outcome ranging spontaneous differentiation metastatic forms poor prognosis. The deep knowledge NB imperative toward development novel therapy. The favourable subset (stage 4S) can spontaneously differentiate neurons or regress benign tumour phenotype. Retinoic Acid (RA) known differentiation-inducing agent actually used In order get new insights molecular mechanism driving neuronal vitro, two-Dimensional Differential In-Gel Electrophoresis (2D-DIGE) analyse was performed on cytosolic nuclear protein expression patterns cells following RA treatment. combination proteomic approach sub-cellular fractionation proteome provides identification 33 differentially expressed proteins during treatment NB. identified have important roles variety pathways may role RA-induced differentiation. results also strength use proteomics discover putative targets cancer. Expression Trk receptors prognostic factor TrkB its ligand BDNF (brain derived neurotrophin factor) are preferentially prognosis, conferring invasive potential as well enhancing therapy resistance. TrkA contrast high good outcome. Galectin-1 (Gal-1), very promising target, involved modulating cell proliferation, death migration found be up-regulated patients aggressive, relapsing Gal-1 down-stream mediator signalling, since espression increased human SY5Y upon activation ectopically (SY5Y-TrkB), but not (SY5Y-TrkA). Functional studies here presented underlined mediate invasion over-expressing cells, thus being activated by BDNF. establishes therapeutic marker high-risk TrkB-expressing