P4-ROLE OF DIPEPTIDYL PEPTIDASE IV IN PERIPHERAL NEUROGENESIS AND NEUROBLASTOMAS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The process of differentiation plays a key role in generation of various cell types during peripheral neuronal development. Perturbation in this process leads to various pathological conditions including the development of tumors such as, neuroblastomas (NB), a child hood cancer. NB forms in the peripheral nerves that provide signals to organs such as the lungs, liver, and heart and that tell the body how to respond to stress. NB produce high levels of growth factors that promote tumor growth. Our work and work by others have identified an enzyme that sits on cell surface and degrades these cancer promoting growth factors. DPPIV is almost absent in NB derived cells compared to normal neuronal cells suggesting that DPPIV is required for maintaining the normal state of the cells, and its loss contributes to tumor development. However, role of DPPIV in development of peripheral nervous system and NB is not known. In the proposed studies, we will investigate the regulation of DPPIV expression during the development of peripheral neurons, understand how DPPIV functions, and determine if DPPIV suppresses the growth of NB cells using both cellular and animal model approaches. Our studies have shown that restoration of DPPIV in NB cells slows down their growth, causes them to become more like normal neurons and also leads to their death. These studies provide insights into the potential contribution of DPPIV to peripheral neural development and in inhibiting development of NB and may open up new avenues for developing novel treatment strategies for NB.