Interactions of KSHV and endothelial cells

KSHV 与内皮细胞的相互作用

基本信息

批准号：
8111133
负责人：
Michael Lagunoff
金额：
$ 26.18万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8111133
关键词：
Acquired Immunodeficiency Syndrome Africa Apoptosis Apoptosis Promoter Cause of Death Cell Surface Receptors Cell Survival Cells Common Neoplasm Data Endothelial Cells Energy-Generating Resources Gene Expression Genes Glycolysis Growth Health Herpesviridae Herpesviridae Infections Highly Active Antiretroviral Therapy Human Herpesvirus 8 Hyperplasia Hypoxia Infection Inhibition of Apoptosis Kaposi Sarcoma Lactic acid Maintenance Malignant Neoplasms Mediating Metabolism Mitochondria Nature Oncogenic Oncogenic Viruses Oxidative Phosphorylation Oxygen Pathogenesis Pathway interactions Patients Phosphorylation Play Production Reporting Role STAT3 gene Signal Pathway Signal Transduction Signal Transduction Pathway Source Spindle Cell Neoplasm Up-Regulation Viral Viral Genes Warburg Effect carcinogenesis cell growth cell transformation cytokine functional outcomes glucose uptake immortalized cell inhibitor/antagonist killings latent infection neoplastic cell receptor response therapeutic target tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Kaposi's Sarcoma (KS) is the most common tumor in AIDs patients and is currently the most commonly reported tumor in regions of Africa. KS tumors can spontaneously regress and KS tumor cells rarely grow out as transformed cells indicating that KS tumors are hyperplasias caused by stimulation of the tumor cell. Kaposi's Sarcoma-associated herpesvirus (KSHV) is an essential etiologic agent for KS. In KS, KSHV is found in the main KS tumor cell, the spindle cell, a cell of endothelial origin. In the KS tumor KSHV is predominantly latent where its limited gene expression leads to many changes in the host cell. KSHV alteration of host signaling pathways common to many types of tumors may be critical for the maintenance of the hyperplasia. Persistent signaling of STAT3 is common in many tumors and is induced by latent KSHV infection of endothelial cells. Most tumors alter the source of their metabolism from oxidative phosphorylation to glycolysis through activation of Hypoxia induced factors. KSHV also activates hypoxia induced factors in endothelial cells. KSHV persistent activation of signaling pathways like STAT3 and the Hypoxia response pathway are likely to play an important role in KS tumorigenesis and might provide important therapeutic targets for KS. PUBLIC HEALTH RELEVANCE: Kaposi's Sarcoma (KS) is the most widespread tumor of AIDS patients and is the most commonly reported tumor in regions of Africa. Kaposi's Sarcoma-associated herpesvirus (KSHV) is an essential agent for the formation of KS. This proposal aims to gain a further understanding of how KSHV alters host cell signaling to induce KS tumors. These pathways may provide therapeutic targets for KS tumor therapy.

描述（由申请人提供）：Kaposi的肉瘤（KS）是艾滋病患者中最常见的肿瘤，目前是非洲地区最常见的肿瘤。 KS肿瘤会自发地回归，KS肿瘤细胞很少生长，因为转化的细胞表明KS肿瘤是由肿瘤细胞刺激引起的增生。 Kaposi与肉瘤相关的疱疹病毒（KSHV）是KS的必不可少的病因。在KS中，KSHV在主KS肿瘤细胞，纺锤体细胞中发现，内皮起源的细胞。在KS肿瘤中，KSHV主要是潜在的，其基因表达有限导致宿主细胞发生了许多变化。多种类型肿瘤常见的宿主信号通路的KSHV改变对于维持增生至关重要。 STAT3的持续信号在许多肿瘤中很常见，并且由内皮细胞的潜在KSHV感染引起。大多数肿瘤通过激活缺氧诱导的因子而将其代谢的来源从氧化磷酸化变为糖酵解。 KSHV还激活了内皮细胞中缺氧引起的因子。 KSHV持续激活STAT3和缺氧反应途径等信号通路可能在KS肿瘤发生中起重要作用，并且可能为KS提供重要的治疗靶标。公共卫生相关性：卡波西的肉瘤（KS）是艾滋病患者最广泛的肿瘤，是非洲地区最常见的肿瘤。卡波西（Kaposi）与肉瘤相关的疱疹病毒（KSHV）是KS形成的必不可少的药物。该建议旨在进一步了解KSHV如何改变宿主细胞信号传导诱导KS肿瘤。这些途径可能为KS肿瘤疗法提供治疗靶标。