COMPARISON OF THE PROTEOMES OF PROLIFERATING AND DIFFERENTIATING NEUROBLASTOMA C

增殖和分化神经母细胞瘤 C 的蛋白质组比较

• 批准号: 8168185
• 负责人: UMADEVI V WESLEY
• 金额: $ 0.35万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168185
• 关键词: Amino Acids; Apoptosis; Biology; Cell Culture Techniques; Cell Line; Cell membrane; Cell surface; Cells; Child; Clinical; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Core Facility; Data; Development; Diagnostic; Dipeptidyl-Peptidase IV; Disease; Faculty; Funding; Grant; Growth; Institution; Label; Malignant Childhood Neoplasm; Molecular Target; Neural Crest; Neuroblastoma; Peptide Hydrolases; Peptides; Peripheral; Peripheral Nervous System; Play; Process; Proliferating; Proteins; Proteome; Proteomics; Research; Research Personnel; Resources; Role; Source; Technology; Therapeutic; Tumor Suppressor Genes; Undifferentiated; United States National Institutes of Health; base; extracellular; member; neoplastic cell; neurodevelopment; novel; outcome forecast; prognostic; protein expression; restoration

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. Perturbation in the normal differentiation process during peripheral neural development leads to neuroblastoma, a childhood cancer of peripheral nervous system. More than 50% of children with neuroblastoma have metastatic or aggressive disease with poor overall prognosis. Thus, identification of novel molecular targets involved in the development of neuroblastoma is of clinical importance. Our studies have shown that expression of a cell surface protease called dipeptidyl peptidase IV (DPPIV) is significantly decreased in neuroblastoma cells as compared to normal neural crest derived cells. Furthermore, restoration of DPPIV expression in neuroblastoma cells leads to their differentiation, apoptosis, and suppression of their tumoigenic potential. It is well established that secreted proteins/peptides play a pivotal role in regulatingthese processes. Interestingly, DPPIV is present on cell plasma membrane as well as in secreted form and DPPIV is shown to regulate the activities and levels of some of the secreted mitogenic peptides. Thus, it is likely that DPPIV functions as tumor suppressor gene by modulating the spectrum of proteins secreted by tumor cells, rendering their microenvironment less supportive of the survival and spread of tumor cells. Thus identification of secreted proteins that are regulated by DPPIV in neuroblastoma cells is of importance. Based on these data, we hypothesize that DPPIV differentially regulates the expression of proteins or peptides with growth inhibitory and stimulatory functions. Our current proposal is aimed at identifying the differentially expressed secreted peptides by employing proteomic technologies. We will adapt stable isotopic labeling with amino acids in cell culture (SILAC) technology to identify and quantify proteins differentially expressed or released into the extracellular media by a pair of undifferentiated and differentiated NB cell lines. These studies will be carried out in collaboration with faculty members of VGN proteomic core facility. Our proposed studies are expected to identify the novel peptides with prognostic, diagnostic and/or therapeutic value. Also, results from the proposed studies may contribute significantly to better understanding of biology of neuroblastoma.

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代表。列出的机构是 对于中心，这不一定是调查员的机构。 外周神经发育过程中正常分化过程中的扰动导致神经母细胞瘤，神经母细胞瘤，这是一种儿童周围神经系统的癌症。超过50％的神经母细胞瘤儿童患有转移性或攻击性疾病，总体预后不佳。因此，鉴定与神经母细胞瘤发展有关的新分子靶标具有临床重要性。我们的研究表明，与正常的神经rest衍生的细胞相比，神经母细胞瘤细胞中称为二肽基肽酶IV（DPPIV）的细胞表面蛋白酶的表达显着降低。此外，神经母细胞瘤细胞中DPPIV表达的恢复会导致其分化，凋亡和抑制其肿瘤潜能。众所周知，分泌的蛋白质/肽在调节这些过程中起关键作用。有趣的是，DPPIV存在于细胞质膜以及分泌的形式上，而DPPIV显示可调节某些分泌有丝分裂肽的活性和水平。因此，DPPIV可能通过调节由肿瘤细胞分泌的蛋白质的光谱来充当肿瘤抑制基因，从而使其微环境对肿瘤细胞的存活和扩散较少支持。因此，在神经母细胞瘤细胞中受DPPIV调控的分泌蛋白质鉴定很重要。基于这些数据，我们假设DPPIV差异地调节具有生长抑制和刺激功能的蛋白质或肽的表达。我们当前的建议旨在通过采用蛋白质组学技术来识别差异表达的分泌肽。我们将在细胞培养（SILAC）技术中使用氨基酸稳定的同位素标记，以通过一对未分化和分化的NB细胞系鉴定和量化差异表达或释放到细胞外培养基中的蛋白质。这些研究将与VGN Proteomic核心设施的教职员工合作进行。我们提出的研究预计将确定具有预后，诊断和/或治疗价值的新肽。此外，拟议研究的结果可能会有助于更好地理解神经母细胞瘤的生物学。