Research Programs Unit, Translational Cancer Biology, University of Helsinki, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), University of Helsinki FIN-00014, Finland.
Research Programs Unit, Translational Cancer Biology, University of Helsinki, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), University of Helsinki FIN-00014, Finland; Foundation for the Finnish Cancer Institute, Helsinki, Finland; Section of Virology, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
Curr Opin Virol. 2017 Oct;26:156-162. doi: 10.1016/j.coviro.2017.09.002. Epub 2017 Oct 12.
Kaposi's sarcoma (KS) is an endothelial tumor causally linked to Kaposi's sarcoma herpesvirus (KSHV) infection. At early stages of KS, inflammation and aberrant neoangiogenesis are predominant, while at late stages the disease is characterized by the proliferation of KSHV-infected spindle cells (SC). Since KSHV infection modifies the endothelial cell (EC) identity, the origin of SCs remains elusive. Yet, pieces of evidence indicate the lymphatic origin. KSHV-infected ECs display increased proliferative, angiogenic and migratory capacities which account for KS oncogenesis. Here we propose a model in which KSHV reprograms the EC identity, induces DNA damage and establishes a dysregulated gene expression program involving interplay of latent and lytic genes allowing continuous reinfection of ECs attracted to the tumor by the secretion of virus-induced cellular factors.
卡波西肉瘤（KS）是一种内皮细胞肿瘤，与卡波西肉瘤疱疹病毒（KSHV）感染有关。在 KS 的早期阶段，炎症和异常新生血管形成占主导地位，而在晚期阶段，疾病的特征是感染 KSHV 的梭形细胞（SC）的增殖。由于 KSHV 感染改变了内皮细胞（EC）的特性，因此 SC 的起源仍然难以捉摸。然而，有证据表明其起源于淋巴管。感染 KSHV 的 EC 表现出增加的增殖、血管生成和迁移能力，这解释了 KS 的肿瘤发生。在这里，我们提出了一个模型，其中 KSHV 重新编程 EC 特性，诱导 DNA 损伤，并建立一个失调的基因表达程序，涉及潜伏和裂解基因的相互作用，允许被病毒诱导的细胞因子吸引到肿瘤中的 EC 持续再感染。
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