Neuroblastoma is the most common extracranial solid tumor in children and is responsible for 15% of pediatric cancer deaths. Metastatic spread of disease is the principal factor associated with poor outcome. These tumors derive from embryonic neural crest cells. Aberrant responses to neural crest growth and differentiation signals are thought to play an important role in determining the malignant phenotype of neuroblastoma tumor cells, however, the molecular mechanisms regulating the proliferation and metastasis of this tumor remain largely unknown. Growth factors, cytokines and chemokines play important roles in tumor proliferation, invasion, and metastasis of neuroblastoma. We cloned a novel secreted molecule, named Neuroblastoma Derived Secreted Protein (NDSP), from our microarray-based analysis of differential gene expression in high risk neuroblastoma tumors. Our preliminary studies have shown that NDSP is highly expressed in neuroblastoma cells, displays a minimal expression profile in normal human tissues, and its encoded protein is secreted into culture media. In addition, we found that NDSP is a Nerve Growth Factor (NGF) responsive gene in neuroblastoma cells. The central hypothesis of this work is that NDSP is a novel diagnostic marker for neuroblastoma and essential for neuroblastoma growth and metastasis. The proposed experiments will test this hypothesis by analyzing the expression pattern and biological role of NDSP in neuroblastoma.
The specific aims of this application are: 1) to determine whether NDSP is a potential biomarker for neuroblastoma; 2) to determine whether NDSP is involved in regulating neuroblastoma tumor formation and dissemination. It is likely that NDSP is not only a potential drug target for therapeutic intervention but also a potential diagnostic biomarker.
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