Neuropeptide Y and Its Receptors in Neuroblastoma
- Determine the expression of neuropeptide Y (NPY) and its receptors (Rs) in human
neuroblastoma (NB) tissues.
- Determine whether BDNF/TrkB and TrkAIII stimulate expression of NPY and its Rs.
- Determine whether NPY mediates BDNF- and TrkAIII-induced NB proliferation and survival.
- Determine neurotrophins' angiogenic actions.
- Identify factors released from NB cells upon NPY stimulation (proteomics).
- Determine whether NPY upregulates expression of the identified proteins in NB and their
Rs in endothelial cells (ECs).
- Test whether inhibition of the identified pathways reduces angiogenic activity of
- Determine the mechanisms of NYP actions and signaling pathways.
- Test whether blocking NPY-Y2/Y5 pathway reduces NB growth and vascularization in vivo.
OUTLINE: Archived tumor tissue and serum samples are analyzed for neuropeptide Y and its
receptors (Y1, Y2, and Y5) expression, neuroblastoma prognostic factors (MYCN, TrkA,
TrkAIII, TrkB, BDNF, and NGF), and angiogenic markers by real-time PCR, IHC, ELISA,
radioimmunoassay (RIA), mitogenic assay, caspase 3/7 activity assay, western blots, liquid
chromatography, tandem mass spectrometry, proteomic assays, and other assays. Results are
then analyzed and compared with patients' clinical data, including stage of disease, its
phenotype, prognostic markers, age and gender, and response to treatment.
Association of high expression of NPY and its Y2/Y5 Rs in NBs with poor outcome of the disease, advanced stage, increased vascularization and other unfavorable prognostic factors, such as TrkB expression and MYCN amplification
Joanna Kitlinska, PhD
Lombardi Cancer Research Center
United States: Federal Government