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

• 批准号: 9238748
• 负责人: David G Meckes
• 金额: $ 34.14万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9238748
• 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; EBV-associated malignancy; Environment; Epstein-Barr virus LMP-1 protein; Etiology; Event; 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; differentiated B cell; 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

 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.