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: 7959689
• 负责人: UMADEVI V WESLEY
• 金额: $ 21.52万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959689
• 关键词: Biology; Cell surface; Cells; Cessation of life; Child; Computer Retrieval of Information on Scientific Projects Database; Development; Dipeptidyl Peptidases; Dipeptidyl-Peptidase IV; Enzymes; Funding; Generations; Grant; Growth; Growth Factor; Health; Heart; Institution; Lead; Lung; Malignant Childhood Neoplasm; Malignant Neoplasms; Neuroblastoma; Neurons; Neurosciences; Organ; Peripheral; Peripheral Nerves; Peripheral Nervous System; Play; Process; Regulation; Research; Research Personnel; Resources; Role; Signal Transduction; Source; United States National Institutes of Health; Work; biological adaptation to stress; cell type; improved; mouse model; nervous system development; neurogenesis; restoration; treatment strategy; 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 nervous system (PNS) development. Perturbation in this process can lead to development of tumors such as neuroblastoma (NB), a childhood cancer. NB forms in the peripheral nerves that provide signals to organs such as the lungs and heart and dictate the body's stress response. NB produces high levels of growth factors that promote tumor growth. One enzyme called dipeptidyl peptidase (DPPIV) that sits on cell surface is known to degrade these cancer-promoting growth factors. However, the role of DPPIV in development of PNS and NB is not known. Our work has shown that DPPIV is present in normal neural cells while almost absent in NB cells, suggesting that DPPIV is required for maintaining the normal state of the cells, and that its loss contributes to tumor development. In support of this idea, our studies show that restoration of DPPIV in NB cells causes them to become more like normal neurons and also leads to their death, thus suppressing their ability to form tumors in a mouse model. We will further investigate the regulation of DPPIV expression during PNS development in order to understand how DPPIV functions, using both cellular and mouse models. Completion of these studies should elucidate the important mechanism involved in PNS and NB development and may advance our understanding of NB biology while providing important clues to improve current treatment strategies to block the growth of NB, which remains a major health problem in children.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 分化过程在周围神经系统（PNS）发育过程中在产生各种细胞类型中起关键作用。 在此过程中，扰动会导致儿童癌（NB）等肿瘤的发展。 NB在周围神经中形成，为肺和心脏等器官提供信号，并决定人体的压力反应。 NB会产生高水平的生长因子，以促进肿瘤生长。 众所周知，一种称为细胞表面上的称为二肽基肽酶（DPPIV）的酶会降低这些促进癌症的生长因子。 但是，DPPIV在PNS和NB发展中的作用尚不清楚。 我们的工作表明，DPPIV存在于正常神经细胞中，而NB细胞中几乎没有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的发展。 为了支持这一想法，我们的研究表明，NB细胞中DPPIV的恢复会导致它们变得更像正常的神经元，并导致其死亡，从而抑制了它们在小鼠模型中形成肿瘤的能力。 我们将进一步研究PNS发育过程中DPPIV表达的调节，以了解DPPIV如何使用细胞和小鼠模型的功能。 这些研究的完成应阐明PNS和NB开发中涉及的重要机制，并可以提高我们对NB生物学的理解，同时提供重要的线索来改善当前的治疗策略以阻止NB的增长，这仍然是儿童的主要健康问题。