Kaposi's sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.

中文翻译：

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PDGFRA通过在血管生成环境中启用KSHV肿瘤发生来定义间充质干细胞卡波济氏肉瘤祖细胞。

卡波济肉瘤（KS）是由KS相关疱疹病毒（KSHV）引起的艾滋病定义癌症。关于KS的未解决的问题是其细胞本体和有利于病毒致癌的条件。我们确定PDGFRA（+）/ SCA-1（+）骨髓源性间充质干细胞（Pα（+）S MSCs）为KS梭形细胞祖细胞，发现典型的KS促血管生成环境条件对于KSHV肉瘤的形成至关重要。这是因为在类似KS的条件下生长会产生抑制的KSHV表观基因组，从而允许在感染的Pα（+）S MSC中表达致癌的KSHV基因。此外，这些生长条件允许KSHV感染的Pα（+）S MSC通过PDGFRA信号传导机制克服KSHV驱动的癌基因诱导的衰老和细胞周期停滞。