Interactions of KSHV and endothelial cells

描述(申请人提供)：卡波西氏肉瘤(KS)是艾滋病患者最常见的肿瘤，目前是非洲地区报道最常见的肿瘤。KS肿瘤可以自发消退，KS肿瘤细胞很少长出转化细胞，这表明KS肿瘤是由肿瘤细胞刺激引起的增生性病变。卡波西肉瘤相关疱疹病毒(KSHV)是KS的重要病原体。在KS中，KSHV存在于主要的KS肿瘤细胞--梭形细胞中，这是一种内皮来源的细胞。在KS肿瘤中，KSHV主要是潜伏的，其有限的基因表达导致宿主细胞的许多变化。KSHV对许多类型肿瘤常见的宿主信号通路的改变可能是维持增殖的关键。STAT3的持续信号在许多肿瘤中很常见，并且是由KSHV潜伏感染内皮细胞诱导的。大多数肿瘤通过激活低氧诱导因子来改变其代谢的来源，从氧化磷酸化到糖酵解。KSHV还能激活血管内皮细胞中的缺氧诱导因子。KSHV持续激活STAT3等信号通路和低氧反应通路可能在KS的发生发展中起重要作用，并可能为KS提供重要的治疗靶点。公共卫生相关性：卡波西氏肉瘤(KS)是艾滋病患者中最常见的肿瘤，也是非洲地区最常见的报告肿瘤。卡波西肉瘤相关疱疹病毒(KSHV)是KS形成的重要致病因子。本研究旨在进一步了解KSHV是如何改变宿主细胞信号从而诱发KS肿瘤的。这些通路可能为KS肿瘤的治疗提供靶点。

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.