In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: A cell and animal model of virally induced Kaposi's sarcoma
In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: A cell and animal model of virally induced Kaposi's sarcoma
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DOI：
10.1016/j.ccr.2007.01.015
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发表时间：
2007-03-01
期刊：
影响因子：
50.3
通讯作者：
Mesri, Enrique A.
中科院分区：
文献类型：
--
作者：
Mutlu, Agata D'Agostino;Cavallin, Lucas E.;Mesri, Enrique A.
将卡波西肉瘤（KS）疱疹病毒（KSHV）细菌人工染色体（KSHVBac 36）转染到小鼠骨髓内皮谱系细胞中产生在小鼠中形成KS样肿瘤的细胞（mECK 36）。mECK 36表达KSHV大部分基因，具有血管生成能力，但在软琼脂中不形成集落。在裸鼠中，mECK 36形成了携带KSHV的血管化梭形细胞肉瘤，其为拉娜+/podoplanin+，过表达VEGF和血管生成素配体;和受体，并显示KSHV和使人联想到KS的宿主转录组。缺失KSHV附加体的mECK 36恢复为非致瘤性。siRNA抑制KSHV vGPCR（一种在mECK 36肿瘤中上调的血管生成基因）可抑制血管生成和致瘤性。这些结果表明，KSHV恶性肿瘤是在体内生长受限和可逆的，定义mECK 36作为KSHV依赖性KS的生物敏感的动物模型。
Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial-lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but they didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands; and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to nontumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene upregulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS.