Exosomal miR-155 Derived from Hepatocellular Carcinoma Cells Under Hypoxia Promotes Angiogenesis in Endothelial Cells
Exosomal miR-155 Derived from Hepatocellular Carcinoma Cells Under Hypoxia Promotes Angiogenesis in Endothelial Cells
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DOI：
10.1007/s10620-018-5380-1
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发表时间：
2019-03-01
影响因子：
3.1
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
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作者：
Matsuura, Yusuke;Wada, Hiroshi;Mori, Masaki
目的本研究旨在阐明缺氧条件下肝细胞癌（HCC）细胞分泌的外泌体是否影响内皮细胞的血管生成。方法将源自人肝癌细胞系的外泌体在缺氧或常氧条件下培养24小时，使用ExoQuick-TC（R）分离，并与HUVEC共培养以评估血管生成活性。我们还评估了 40 名 HCC 患者的外泌体中 miR-155 的表达。结果缺氧下的外泌体显着增强了 HUVEC 的管形成。在缺氧条件下，细胞和外泌体 miR-155 均显着上调。 HCC细胞中miR-155的敲低减弱了缺氧条件下外泌体对HUVEC管形成的促进作用，术前血浆中外泌体miR-155的高表达与早期复发显着相关。结论这些结果表明，缺氧条件下来源于HCC细胞的外泌体诱导HUVEC管形成，并且外泌体miR-155可能影响血管生成 HCC 中的活动。
PurposeIn this study, we aim to clarify whether exosomes secreted from hepatocellular carcinoma (HCC) cells under hypoxia affect angiogenesis in endothelial cells.MethodsExosomes derived from human liver cancer cell lines were cultured under hypoxic or normoxic conditions for 24h, isolated using ExoQuick-TC (R), and co-cultured with HUVECs to evaluate angiogenic activity. We also evaluated the expression of miR-155 in the exosomes from 40 patients with HCC.ResultsExosomes under hypoxia remarkably enhanced tube formation of HUVECs. Both cellular and exosomal miR-155 were significantly up-regulated under hypoxic conditions. Knockdown of miR-155 in HCC cells attenuated the promotion of tube formation by exosomes under hypoxia in HUVECs, and high expression of exosomal miR-155 in preoperative plasma was significantly correlated with early recurrence.ConclusionThese results suggest that exosomes derived from HCC cells under hypoxia induce tube formation of HUVECs and that exosomal miR-155 may affect angiogenic activity in HCC.