Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model.
Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model.
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来自疟原虫感染宿主的外泌体抑制小鼠Lewis肺癌模型中的肿瘤血管生成
DOI：
10.1038/oncsis.2017.52
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发表时间：
2017-06-26
期刊：
影响因子：
6.2
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Yang Y;Liu Q;Lu J;Adah D;Yu S;Zhao S;Yao Y;Qin L;Qin L;Chen X
先前研究疟疾感染和肿瘤进展之间的相互作用的研究表明，疟疾感染可以增强荷瘤小鼠对肿瘤的宿主免疫反应。外泌体可能在感染过程中传播病原性宿主衍生分子中发挥关键作用，因为一些研究已经表明细胞外囊泡参与细胞间通讯并发挥作用。然而，疟原虫感染期间产生的外泌体在肿瘤生长、进展和血管生成中的作用尚未在动物或临床中研究。为了验证这一假设，我们设计了一种动物模型来从小鼠中产生和分离外泌体，这些外泌体随后用于治疗肿瘤。肿瘤内注射来源于疟原虫感染小鼠血浆的外来体显著降低了小鼠中的刘易斯肺癌生长。我们进一步将分离的外泌体与内皮细胞共培养，观察到内皮细胞中VEGFR 2的表达和迁移显著降低。有趣的是，与来自对照小鼠的外泌体相比，在来自感染疟原虫的小鼠的血浆的外泌体中检测到高水平的微小RNA（miRNA）16/322/497/17。我们观察到在内皮细胞中miRNA 16/322/497/17的过表达对应于VEGFR 2表达的降低，血管生成的抑制和miRNA 16/322/497/17的抑制显著减轻了这些作用。这些数据为疟原虫感染与肺癌生长和血管生成之间的相互作用提供了新的科学证据。
Previous research to investigate the interaction between malaria infection and tumor progression has revealed that malaria infection can potentiate host immune response against tumor in tumor-bearing mice. Exosomes may play key roles in disseminating pathogenic host-derived molecules during infection because several studies have shown the involvement and roles of extracellular vesicles in cell–cell communication. However, the role of exosomes generated during Plasmodium infection in tumor growth, progression and angiogenesis has not been studied either in animals or in the clinics. To test this hypothesis, we designed an animal model to generate and isolate exosomes from mice which were subsequently used to treat the tumor. Intra-tumor injection of exosomes derived from the plasma of Plasmodium-infected mice provided significantly reduced Lewis lung cancer growth in mice. We further co-cultured the isolated exosomes with endothelial cells and observed significantly reduced expression of VEGFR2 and migration in the endothelial cells. Interestingly, high level of micro-RNA (miRNA) 16/322/497/17 was detected in the exosomes derived from the plasma of mice infected with Plasmodium compared with those from control mice. We observed that overexpression of the miRNA 16/322/497/17 in endothelial cell corresponded with decreased expression of VEGFR2, inhibition of angiogenesis and inhibition of the miRNA 16/322/497/17 significantly alleviated these effects. These data provide novel scientific evidence of the interaction between Plasmodium infection and lung cancer growth and angiogenesis.
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影响因子：
5.6
作者：
Finnerty JR;Wang WX;Hébert SS;Wilfred BR;Mao G;Nelson PT
通讯作者：
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作者：
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DOI：
10.1073/pnas.0800121105
发表时间：
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影响因子：
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通讯作者：
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