CD147 and downstream ADAMTSs promote the tumorigenicity of Kaposi's sarcoma-associated herpesvirus infected endothelial cells.
CD147 and downstream ADAMTSs promote the tumorigenicity of Kaposi's sarcoma-associated herpesvirus infected endothelial cells.
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CD147 和下游 ADAMTS 促进卡波西肉瘤相关疱疹病毒感染内皮细胞的致瘤性
DOI：
10.18632/oncotarget.6584
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发表时间：
2016-01-26
期刊：
影响因子：
--
通讯作者：
Qin Z
中科院分区：
文献类型：
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作者：
Dai L;Trillo-Tinoco J;Chen Y;Bonstaff K;Del Valle L;Parsons C;Ochoa AC;Zabaleta J;Toole BP;Qin Z
卡波西氏肉瘤相关疱疹病毒（KSHV）是几种人类癌症的病因，包括卡波西氏肉瘤（KS），它优先出现在免疫功能低下的患者中，缺乏有效的治疗选择。我们之前已经证明KSHV或病毒蛋白LANA上调糖蛋白CD147，从而诱导原代内皮细胞侵袭。在当前的研究中，我们使用Illumina微阵列分析确定了kshv感染内皮细胞中由CD147控制的全局网络。在下游基因中，两个特异性金属蛋白酶ADAMTS1和adamts9在AIDS-KS组织中强烈表达，并通过上调IL-6和VEGF参与kshv感染的内皮细胞侵袭。通过使用ks样裸鼠模型，我们发现靶向CD147和下游ADAMTSs在体内显著抑制kshv诱导的肿瘤发生。综上所述，靶向CD147和相关蛋白可能是治疗这些kshv相关恶性肿瘤的一种有希望的治疗策略。
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up-regulation of IL-6 and VEGF. By using a KS-like nude mouse model, we found that targeting CD147 and downstream ADAMTSs significantly suppressed KSHV-induced tumorigenesis in vivo. Taken together, targeting CD147 and associated proteins may represent a promising therapeutic strategy against these KSHV-related malignancies.