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

P4-二肽基肽酶 IV 在外周神经发生和神经母细胞瘤中的作用

• 批准号: 7609873
• 负责人: UMADEVI V WESLEY
• 金额: $ 21.77万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609873
• 关键词: Animal Model; Cell surface; Cells; Cessation of life; Child; Computer Retrieval of Information on Scientific Projects Database; Condition; Development; Dipeptidyl Peptidases; Enzymes; Funding; Generations; Grant; Growth; Growth Factor; Heart; Institution; Liver; Lung; Malignant Neoplasms; Neuroblastoma; Neurons; Organ; Peripheral; Peripheral Nerves; Peripheral Nervous System; Play; Process; Regulation; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Stress; United States National Institutes of Health; Work; cell type; insight; neurodevelopment; neurogenesis; novel; restoration; tumor; tumor growth

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 分化过程在周围神经元发育过程中各种细胞类型的产生中起着关键作用。这一过程中的扰动会导致各种病理状况，包括肿瘤的发展，例如神经母细胞瘤（NB），一种儿童癌症。 NB 形成于周围神经中，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 产生高水平的生长因子，促进肿瘤生长。我们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，并且它的缺失有助于肿瘤的发展。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，我们将研究外周神经元发育过程中 DPPIV 表达的调节，了解 DPPIV 的功能，并使用细胞和动物模型方法确定 DPPIV 是否抑制 NB 细胞的生长。 我们的研究表明，NB 细胞中 DPPIV 的恢复会减慢它们的生长，使它们变得更像正常神经元，并导致它们死亡。这些研究深入了解了 DPPIV 对周围神经发育和抑制 NB 发展的潜在贡献，并可能为开发新的 NB 治疗策略开辟新途径。