PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype
PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype
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DOI：
10.1182/blood-2007-04-085555
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发表时间：
2008-03-01
期刊：
影响因子：
20.3
通讯作者：
Camussi, Giovanni
中科院分区：
文献类型：
--
作者：
Fonsato, Valentina;Buttiglieri, Stefano;Camussi, Giovanni
在本研究中，我们评估是否感染微血管内皮细胞（HMEC）与HHV-8可以触发PAX 2癌基因的表达和PAX 2蛋白是否参与HHV-8诱导的HMEC的转化。我们发现，HHV-8感染诱导HMECS中PAX 2基因和PAX 2蛋白的表达，但不能诱导PAX 2蛋白在稳定转染PAX 2反义核酸的HMEC-AS中表达。HHV-8感染的HMEC而不是HMEC-AS获得了促侵袭促粘附特性，增强了存活率和体外血管生成，表明PAX 2表达与HHV-8感染引发的效应之间存在相关性。当通过PAX 2正义基因稳定转染或通过HHV-8感染将表达HMEC的PAX 2植入严重联合免疫缺陷（SCID）小鼠体内时，观察到类似KS的血管生成和增殖性病变增强。HHV-8感染的HMEC-AS不能诱导血管生成和KS样病变。这些结果表明，PAX 2的表达所需的促血管生成和促浸润的变化诱导HHV-8感染HMEC。结论：HHV-8感染可能通过诱导PAX 2癌基因的表达激活HMEC中的胚胎血管生成程序。
In the present study, we evaluated whether infection of microvascular endothelial cells (HMECs) with HHV-8 can trigger the expression of PAX2 oncogene and whether PAX2 protein is involved in HHV-8-induced transformation of HMECs. We found that HHV-8 infection induced the expression of both the PAX2 gene and PAX2 protein in HMECS but failed to induce PAX2 protein in HMECs stably transfected with PAX2 antisense (HMEC-AS). HHV-8-infected HMECs but not HMEC-AS acquired proinvasive proadhesive properties, enhanced survival and in vitro angiogenesis, suggesting a correlation between PAX2 expression and the effects triggered by HHV-8 infection. When HMEC-expressing PAX2 by stable transfection with PAX2 sense gene or by HHV-8 infection were implanted in vivo in severe combined immunodeficient (SCID) mice, enhanced angiogenesis and proliferative lesions resembling KS were observed. HHV-8-infected HMEC-AS failed to induce angiogenesis and KS-like lesions. These results suggest that the expression of PAX2 is required for the proangiogenic and proinvasive changes induced by HHV-8 infection in HMECs. In conclusion, HHV-8 infection may activate an embryonic angiogenic program in HMECs by inducing the expression of PAX2 oncogene.