Neuroblastoma progression

Neuroblastoma (NB) is derived from sympatho-adrenal progenitor cells that migrate from the neural crest into target regions of the embryo. NB is mostly located along the sympathetic trunk ganglia and in the adrenal medulla. The spectrum of the disease ranges from complete spontaneous regression to malignant progression into stage 4, with 5-year survival rates of less than 30%. Partial differentiation into ganglioneuroblastoma is another developmental pathway. The most critical molecular predictor for the behaviour and treatment of NB is the MYCN protooncogene. Up-regulation or amplification (up to 100x) of MYCN characterizes highly aggressive tumors and poor outcome despite intensive treatment. Staging of NB is performed according to the International Neuroblastoma Staging System (INSS). Stage 1 and 2 NBs are localized tumors, which have grown across the midline in stage 2. Metastasis to regional and systemic lymph nodes as well as bone marrow characterizes stages 3 and 4, respectively, indicating active interactions with the lymphovascular system. We are studying ligand-receptor interactions between molecules expressed by NB cells and lymphatic endothelium, and we suggest that mechanisms, which are active during neural crest cell migration, also guide neuroblastoma cells during their metastatic dissemination.