UCL Cancer Institute, 72 Huntley Street, University College London, London WC1E 6BT, UK.
Trends Cell Biol. 2013 Sep;23(9):421-32. doi: 10.1016/j.tcb.2013.04.001. Epub 2013 May 17.
Kaposi's sarcoma (KS) is the most common malignancy in untreated HIV patients. KS is characterised by abnormal neoangiogenesis, inflammation, and proliferation of tumour cells [KS spindle cells (SCs)]. Kaposi's sarcoma-associated herpesvirus (KSHV) is the aetiological agent of KS. KS SCs are the predominant KSHV-infected cells in KS lesions. In this review, we report advances in understanding of the cellular origin of the KS SC, a contentious topic in KSHV research. KS SCs are now known to be of endothelial cell (EC) origin, phenotypically most similar to lymphatic ECs (LECs), but poorly differentiated. We focus on recent insights into KSHV's ability to exploit the normal differentiation pathway and intrinsic plasticity of ECs, through manipulation of EC-specific transcriptional regulators [i.e., prospero homeobox 1 (PROX1) and MAF] and discuss how this may contribute to viral persistence and KS sarcomagenesis.
卡波西肉瘤（KS）是未经治疗的 HIV 患者中最常见的恶性肿瘤。KS 的特征是异常的新血管生成、炎症和肿瘤细胞的增殖[KS 梭形细胞（SCs）]。卡波济肉瘤相关疱疹病毒（KSHV）是 KS 的病因。KS SCs 是 KS 病变中主要感染 KSHV 的细胞。在这篇综述中，我们报告了对 KS SC 细胞起源的理解的进展，这是 KSHV 研究中的一个有争议的话题。KS SCs 现在被认为起源于内皮细胞（EC），表型上与淋巴管内皮细胞（LECs）最相似，但分化不良。我们重点关注最近对 KSHV 利用 EC 正常分化途径和内在可塑性的能力的深入了解，通过操纵 EC 特异性转录调节剂[即 prosopo 同源盒 1（PROX1）和 MAF]，并讨论这如何有助于病毒持续存在和 KS 肉瘤形成。
