Interactions of KSHV and endothelial cells

描述（申请人提供）：卡波西肉瘤（Kaposi’s Sarcoma， KS）是艾滋病患者中最常见的肿瘤，也是目前非洲地区报道最多的肿瘤。KS肿瘤可以自发退化，KS肿瘤细胞很少以转化细胞的形式生长出来，说明KS肿瘤是由于肿瘤细胞受到刺激而引起的增生。卡波西肉瘤相关疱疹病毒（KSHV）是KS的重要病原体。在KS中，KSHV主要存在于KS肿瘤细胞梭形细胞中，梭形细胞是一种内皮细胞。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发生许多变化。KSHV对宿主信号通路的改变在许多类型的肿瘤中都很常见，这可能是维持增生的关键。STAT3的持续信号在许多肿瘤中很常见，并由内皮细胞的潜伏KSHV感染诱导。大多数肿瘤通过激活缺氧诱导因子将其代谢来源从氧化磷酸化转变为糖酵解。KSHV还能激活内皮细胞中的缺氧诱导因子。KSHV持续激活STAT3等信号通路和缺氧反应通路可能在KS肿瘤发生中发挥重要作用，并可能为KS提供重要的治疗靶点。公共卫生相关性：卡波西肉瘤（KS）是艾滋病患者中最广泛的肿瘤，也是非洲地区最常报道的肿瘤。卡波西肉瘤相关疱疹病毒（KSHV）是KS形成的重要因子。本研究旨在进一步了解KSHV如何改变宿主细胞信号从而诱导KS肿瘤。这些途径可能为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.