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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在外周神经元发育过程中，分化过程在各种细胞类型的产生中起关键作用。该过程中的扰动导致各种病理状况，包括肿瘤的发展，例如神经母细胞瘤（NB）、儿童癌症。NB在外周神经中形成，这些神经向肺、肝和心脏等器官提供信号，并告诉身体如何应对压力。NB产生促进肿瘤生长的高水平生长因子。我们的工作和其他人的工作已经确定了一种位于细胞表面并降解这些促癌生长因子的酶。与正常神经元细胞相比，NB衍生的细胞中几乎不存在DPPIV，这表明DPPIV是维持细胞正常状态所必需的，并且其损失有助于肿瘤发展。然而，DPPIV在周围神经系统和NB发育中的作用尚不清楚。在拟议的研究中，我们将调查DPPIV表达的调节过程中的外周神经元的发展，了解DPPIV的功能，并确定DPPIV是否抑制NB细胞的生长，使用细胞和动物模型的方法。 我们的研究表明，NB细胞中DPPIV的恢复减缓了它们的生长，使它们变得更像正常神经元，并导致它们的死亡。这些研究为DPPIV对周围神经发育和抑制NB发展的潜在贡献提供了见解，并可能为开发NB的新治疗策略开辟新途径。

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.