open access

https://doi.org/10.14943/doctoral.k11267

https://hdl.handle.net/2115/56322

がん細胞由来微小胞がエンドサイトーシスを介して血管内皮細胞に血管新性能をもたらす

英語

2014-03-25

Hokkaido University

Citation: Kawamoto T, Ohga N, Akiyama K, Hirata N, Kitahara S, et al. (2012) Tumor-Derived Microvesicles Induce Proangiogenic Phenotype in Endothelial Cells via Endocytosis. PLoS ONE 7(3): e34045. doi:10.1371/journal.pone.0034045

BACKGROUND: 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.METHODOLOGY/PRINCIPAL FINDINGS: 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.CONCLUSION: 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.

2014-03-25

甲第11267号

博士(歯学)

(主査) 教授 進藤 正信, 教授 鄭 漢忠, 特任准教授 樋田 京子

歯学研究科（口腔医学専攻）

博士論文

Version of Record

Creative Commons Attribution 3.0 Unported

© 2012 Kawamoto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.