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Modulation of Host Cell Exosome Content and Function by EBV LMP1

EBV LMP1 对宿主细胞外泌体含量和功能的调节

基本信息

批准号：
9896794
负责人：
David G Meckes
金额：
$ 40.64万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9896794
关键词：
Automobile Driving B cell differentiation B lymphocyte immortalization Biological Blood Breast Cancer Cell Cancer Etiology Cell Proliferation Cells Coculture Techniques Communication Culture Techniques Data Development Diagnostic Disease Disease Progression Dominant-Negative Mutation Environment Epstein-Barr Virus-Related Malignant Neoplasm Epstein-Barr virus LMP-1 protein Etiology Event Exposure to Goals Growth Human Human Herpesvirus 4 Immune In Vitro Liquid substance MAP Kinase Gene Malignant Neoplasms Mass Spectrum Analysis Mediating Membrane Microdomains Membrane Proteins Messenger RNA MicroRNAs Molecular Multivesicular Body Oncogenes Oncogenic Oncogenic Viruses PI3K/AKT Pathogenesis Pathway interactions Patients Phenotype Plasmablast Process Property Proteins Proteome Proteomics Proto-Oncogene Proteins c-akt Role Route Saliva Signal Pathway Signal Transduction Signal Transduction Pathway Signaling Molecule Technology Testing Tumor Cell Invasion Urine Viral Viral Oncogene Viral Proteins Virus angiogenesis base cancer cell cell growth cell transformation chemical genetics combat deep sequencing design exosome experimental study extracellular vesicles genetic inhibitor infected B cell intercellular communication knock-down metaplastic cell transformation migration mutant novel therapeutics phosphoproteomics public health relevance response trafficking transmission process tumor tumor microenvironment tumorigenesis vesicular release

项目摘要

DESCRIPTION (provided by applicant): Exosomes are small vesicles released at high levels from cancer cells that are important modifiers of the tumor environment and contribute to disease progression. Exosomes contain molecular information about their cells of origin and can be isolated from many biological fluids including blood, urine, and saliva. It has recently been discovered that exosomes from breast cancer cells or the blood of patients with the disease can cause non- cancerous cells to form tumors. These findings suggest a critical role of exosomes in cancer development or disease progression, and create new opportunities for exosome-based diagnostics and therapies. Based on data from our studies and others, it is also becoming clear that cancer causing viruses utilize and modify the host cell exosome pathway, and these changes may contribute to disease. For example, cells infected with the Epstein-Barr virus (EBV), a human tumor virus, release exosomes that are enriched in viral products like the major viral oncogene latent membrane protein 1 (LMP1) and virally-encoded miRNAs. We have previously shown that LMP1 alters the cargo of exosomes released from infected cells and that these LMP1-modifed exosomes can exert oncogenic signaling functions on neighboring uninfected cells. In spite of the importance of inter-cellular transmission of LMP1-modifeid exosomes, very little is known about how this viral protein actually enters and manipulates the host exosome pathway. The overall goal of these studies is to determine the mechanisms that LMP1 drives exosome content reorganization and alters the functions of exosomes. We hypothesize that LMP1 exosomal trafficking modulates the components and biological properties of exosomes by altering endocytic routes and membrane microdomains. To test this, we aim to: 1.) investigate the mechanism through which LMP1 alters exosome components; 2.) determine the functions of LMP1-modified exosomes in intracellular communication and cellular transformation.

描述（由申请人提供）：外泌体是癌细胞高水平释放的小囊泡，是肿瘤环境的重要调节剂并有助于疾病进展。外泌体含有有关其来源细胞的分子信息，可以从许多生物液体中分离出来，包括血液、尿液和唾液。最近发现，来自乳腺癌细胞或乳腺癌患者血液的外泌体可以导致非癌细胞形成肿瘤。这些发现表明外泌体在癌症发生或疾病进展中发挥着关键作用，并为基于外泌体的诊断和治疗创造了新的机会。根据我们和其他研究的数据，越来越清楚的是，致癌病毒利用并修改宿主细胞外泌体途径，这些变化可能导致疾病。例如，感染人类肿瘤病毒 Epstein-Barr 病毒 (EBV) 的细胞会释放富含病毒产物的外泌体，例如主要病毒致癌基因潜伏膜蛋白 1 (LMP1) 和病毒编码的 miRNA。我们之前已经证明，LMP1 改变了受感染细胞释放的外泌体的货物，并且这些 LMP1 修饰的外泌体可以对邻近的未感染细胞发挥致癌信号传导功能。尽管 LMP1 修饰的外泌体的细胞间传播很重要，但人们对这种病毒蛋白实际上如何进入并操纵宿主外泌体途径知之甚少。这些研究的总体目标是确定 LMP1 驱动外泌体内容重组和改变外泌体功能的机制。我们假设 LMP1 外泌体运输通过改变内吞途径和膜微区来调节外泌体的成分和生物学特性。为了测试这一点，我们的目标是：1.) 研究 LMP1 改变外泌体成分的机制； 2.) 确定 LMP1 修饰的外泌体在细胞内通讯和细胞转化中的功能。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer's disease-like phenotypes in a preclinical mouse model.

间充质干细胞衍生的细胞外囊泡在临床前小鼠模型中改善阿尔茨海默氏病的表型。

DOI：
10.7150/thno.62069
发表时间：
2021
期刊：
Theranostics
影响因子：
12.4
作者：
Cone AS;Yuan X;Sun L;Duke LC;Vreones MP;Carrier AN;Kenyon SM;Carver SR;Benthem SD;Stimmell AC;Moseley SC;Hike D;Grant SC;Wilber AA;Olcese JM;Meckes DG Jr
通讯作者：
Meckes DG Jr

Multiplex protein profiling method for extracellular vesicle protein detection.