Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis.
Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis.
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DOI：
10.1371/journal.pone.0034045
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hida K
中科院分区：
文献类型：
--
作者：
Kawamoto T;Ohga N;Akiyama K;Hirata N;Kitahara S;Maishi N;Osawa T;Yamamoto K;Kondoh M;Shindoh M;Hida Y;Hida K
越来越多的证据表明，肿瘤内皮细胞(TEC)不同于正常内皮细胞(NEC)。我们之前的报告也表明，TEC与NEC是不同的。例如，TEC具有染色体异常和促血管生成特性，如高运动性和增殖活性。然而，TEC获得特定特征的机制仍不清楚。为了探讨这一机制，我们重点研究了肿瘤来源的微囊泡(TMV)。最近的研究表明，TMV含有多种生物活性分子，影响肿瘤微环境中的正常基质细胞。然而，TMV的大部分作用机制仍不清楚。我们发现从肿瘤细胞中分离出来的TMV是通过内吞作用被NEC摄取的。此外，我们还发现TMV通过激活肌醇磷脂3-激酶/Akt通路促进NEC的随机运动和小管的形成。此外，内吞抑制剂DATORE可抑制TMV诱导的上述效应。我们的结果表明，TMV可以部分地通过内吞作用赋予NEC促血管生成特性。我们首次发现TMV的内吞作用有助于肿瘤血管生成。这些发现为肿瘤治疗和肿瘤微环境中TMV介导的肿瘤与内皮细胞之间的串扰提供了新的见解。
Increasing evidence indicates that tumor endothelial cells (TEC) differ from normal endothelial cells (NEC). Our previous reports also showed that TEC were different from NEC. For example, TEC have chromosomal abnormality and proangiogenic properties such as high motility and proliferative activity. However, the mechanism by which TEC acquire a specific character remains unclear. To investigate this mechanism, we focused on tumor-derived microvesicles (TMV). Recent studies have shown that TMV contain numerous types of bioactive molecules and affect normal stromal cells in the tumor microenvironment. However, most of the functional mechanisms of TMV remain unclear. Here we showed that TMV isolated from tumor cells were taken up by NEC through endocytosis. In addition, we found that TMV promoted random motility and tube formation through the activation of the phosphoinositide 3-kinase/Akt pathway in NEC. Moreover, the effects induced by TMV were inhibited by the endocytosis inhibitor dynasore. Our results indicate that TMV could confer proangiogenic properties to NEC partly via endocytosis. We for the first time showed that endocytosis of TMV contributes to tumor angiogenesis. These findings offer new insights into cancer therapies and the crosstalk between tumor and endothelial cells mediated by TMV in the tumor microenvironment.
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影响因子：
8.8
作者：
Kurosu, T.;Ohga, N.;Hida, Y.;Maishi, N.;Akiyama, K.;Kakuguchi, W.;Kuroshima, T.;Kondo, M.;Akino, T.;Totsuka, Y.;Shindoh, M.;Higashino, F.;Hida, K.
通讯作者：
Hida, K.
影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
影响因子：
11.2
作者：
Hida, K;Hida, Y;Klagsbrun, M
通讯作者：
Klagsbrun, M
DOI：
10.1073/pnas.0804543106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Al-Nedawi, Khalid;Meehan, Brian;Rak, Janusz
通讯作者：
Rak, Janusz
DOI：
10.1073/pnas.1017667108
发表时间：
2011-03-22
影响因子：
11.1
作者：
Antonyak, Marc A.;Li, Bo;Cerione, Richard A.
通讯作者：
Cerione, Richard A.