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.

这个子项目是许多研究子项目中的一个 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。 周围神经发育过程中正常分化过程的干扰导致神经母细胞瘤，一种周围神经系统的儿童癌症。超过50%的儿童神经母细胞瘤有转移性或侵袭性疾病，总体预后不良。因此，识别参与神经母细胞瘤发展的新分子靶点具有临床重要性。我们的研究表明，与正常神经嵴衍生细胞相比，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著降低。此外，在神经母细胞瘤细胞中DPPIV表达的恢复导致其分化、凋亡和其致瘤潜能的抑制。分泌蛋白/肽在调节这些过程中起着关键作用。有趣的是，DPPIV以分泌形式存在于细胞质膜上，并且显示DPPIV调节一些分泌的促有丝分裂肽的活性和水平。因此，DPPIV很可能通过调节肿瘤细胞分泌的蛋白质谱，使其微环境不太支持肿瘤细胞的存活和扩散，从而发挥肿瘤抑制基因的功能。因此，鉴定神经母细胞瘤细胞中受DPPIV调控的分泌蛋白具有重要意义。基于这些数据，我们假设DPPIV差异调节具有生长抑制和刺激功能的蛋白质或肽的表达。我们目前的建议是旨在确定差异表达的分泌肽，采用蛋白质组学技术。我们将采用稳定同位素标记与氨基酸在细胞培养（SILAC）技术，以确定和定量蛋白质差异表达或释放到细胞外介质的一对未分化和分化的NB细胞系。这些研究将与VGN蛋白质组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新的肽与预后，诊断和/或治疗价值。此外，拟议的研究结果可能有助于更好地了解神经母细胞瘤的生物学。