Angiopoietin-like 4: a novel molecular hallmark in oral Kaposi's sarcoma.
Angiopoietin-like 4: a novel molecular hallmark in oral Kaposi's sarcoma.
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DOI：
10.1016/j.oraloncology.2011.02.018
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发表时间：
2011-05
期刊：
影响因子：
4.8
通讯作者：
Montaner, Silvia
中科院分区：
文献类型：
--
作者：
Hu, Jiadi;Jham, Bruno C.;Ma, Tao;Friedman, Eitan R.;Ferreira, Leticia;Wright, John M.;Accurso, Brent;Allen, Carl M.;Basile, John R.;Montaner, Silvia
关键词：
卡波西肉瘤（KS）仍然是艾滋病毒感染者口腔癌的最常见原因之一。KS相关疱疹病毒（KSHV/HHV 8）感染是疾病发展的必要事件。新出现的证据表明，KSHV感染血管内皮（或内皮祖细胞）细胞，促进KS肿瘤（或梭形）细胞的形成。这些细胞产生血管生成生长因子和细胞因子，促进血管生成失调和大量水肿，这是这种不寻常的血管肿瘤的特征。这些分泌因子的中心是有效的内皮细胞有丝分裂原，血管内皮生长因子（VEGF）。事实上，VEGF已被证明是KSHV发病机制中的关键参与者，并且是KS病变的分子标志。我们最近发现，第二个血管生成因子，血管生成素样4（ANGPTL 4），也可能在KS发展中发挥关键作用。在这里，我们证明了ANGPTL 4直接和间接地被KSHV癌基因vGPCR上调。我们进一步表明，ANGPTL 4是口腔KS病变的分子标志。事实上，在更多的肿瘤细胞和更多的活检标本中观察到这种蛋白质的表达，而不是在口服KS中VEGF的表达（分别为23/25或92%对19/25或76%）。这些令人惊讶的结果支持ANGPTL 4在卡波西肉瘤发生中的关键作用，并进一步表明这种血管生成因子可能为口腔KS患者提供新的诊断和治疗标志物。
Kaposi’s sarcoma (KS) remains among the most common causes of oral cancer in HIV-infected individuals. Infection with the KS-associated herpesvirus (KSHV/HHV8) is a necessary event for disease development. Emerging evidence suggests that KSHV infects vascular endothelial (or endothelial progenitor) cells promoting the formation of the KS tumor (or spindle) cell. These cells elaborate angiogenic growth factors and cytokines that promote the dysregulated angiogenesis and profuse edema that characterizes this unusual vascular tumor. Central among these secreted factors is the potent endothelial cell mitogen, vascular endothelial growth factor (VEGF). Indeed, VEGF has proven to be a key player in KSHV pathogenesis and is a molecular hallmark of KS lesions. We have recently shown that a second angiogenic factor, Angiopoietin-like 4 (ANGPTL4), may also play a critical role in KS development. Here we demonstrate that ANGPTL4 is upregulated both directly and indirectly by the KSHV oncogene, vGPCR. We further show that ANGPTL4 is a molecular hallmark of oral KS lesions. Indeed, expression of this protein was observed in more tumor cells and in more biopsies specimens than expression of VEGF (23/25 or 92% vs. 19/25 or 76%, respectively) in oral KS. These surprising results support a key role for ANGPTL4 in Kaposi’s sarcomagenesis and further suggest that this angiogenic factor may provide a novel diagnostic and therapeutic marker for oral KS patients.
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