KSHV activation of VEGF secretion and invasion for endothelial cells is mediated through viral upregulation of emmprin-induced signal transduction.
KSHV activation of VEGF secretion and invasion for endothelial cells is mediated through viral upregulation of emmprin-induced signal transduction.
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DOI：
10.1002/ijc.26428
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发表时间：
2012-08-15
影响因子：
6.4
通讯作者：
Parsons, Chris
中科院分区：
文献类型：
--
作者：
Dai, Lu;Bratoeva, Momka;Toole, Bryan P.;Qin, Zhiqiang;Parsons, Chris
卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤（KS）的病原体，卡波西肉瘤是在免疫抑制的情况下产生的最常见的肿瘤之一。KS病变的标志包括KSHV感染的内皮细胞谱系和新血管生成。由KSHV感染的细胞在肿瘤微环境中分泌的促迁移因子促进内皮细胞（EC）迁移和血管生成，但是针对这些途径的现有方法未被广泛用于KS。这强调了需要额外的表征KSHV-宿主相互作用相关的EC发病机制，以确定新的治疗靶点。我们最近发现，从头感染KSHV促进EC入侵通过上调emmprin-一种多功能糖蛋白，以前显示诱导肿瘤细胞的侵袭和区域血管生成，通过上调信号转导和促进肿瘤间质的相互作用。本研究旨在确定内皮细胞侵袭KSHV感染的细胞是否通过激活特定的信号转导途径和促血管生成因子诱导。我们发现，KSHV激活emmprin诱导PI 3 K/Akt-和丝裂原活化蛋白激酶（MAPK）依赖的血管内皮生长因子（VEGF）的分泌。此外，内皮细胞的侵袭是由emmprin依赖的PI 3 K/Akt和MAPK激活VEGF诱导的。这些发现支持了靶向细胞外基质金属蛋白酶诱导因子在KS微环境中减少VEGF分泌和EC迁移的潜在效用。
The Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma (KS)—one of the most common tumors arising in the setting of immune suppression. Hallmarks of KS lesions include KSHV-infected cells of endothelial lineage and neoangiogenesis. Pro-migratory factors secreted in the tumor microenvironment by KSHV-infected cells promote endothelial cell (EC) migration and angiogenesis, but existing approaches targeting these pathways are not widely utilized for KS. This underscores the need for additional characterization of KSHV-host interactions relevant to EC pathogenesis to identify new therapeutic targets. We recently demonstrated that de novo infection by KSHV promotes EC invasion through upregulation of emmprin—a multifunctional glycoprotein previously shown to induce tumor cell invasion and regional angiogenesis through upregulation of signal transduction and promotion of tumor-stroma interactions. The present study was undertaken to determine whether EC invasion for KSHV-infected cells is induced through activation of specific signal transduction pathways and pro-angiogenic factors by emmprin. We found that KSHV activation of emmprin induces PI3K/Akt- and mitogen-activated protein kinase (MAPK)-dependent secretion of vascular endothelial growth factor (VEGF). Moreover, EC invasion following de novo infection is induced by emmprin-dependent PI3K/Akt and MAPK activation of VEGF. These findings support the potential utility of targeting emmprin for reducing VEGF secretion and EC migration in the KS microenvironment.
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影响因子：
6.4
作者：
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DOI：
10.1615/jenvironpatholtoxicoloncol.v25.i1-2.160
发表时间：
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影响因子：
2.4
作者：
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通讯作者：
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