キタハラ　シユウジ   KITAHARA Shuji   北原　秀治    所属   研究施設 研究施設    職種   特任准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：19326203/19326203
掲載区分	国外
巻・号・頁	7(3),pp.e34045
著者・共著者	Kawamoto Taisuke, Ohga Noritaka, Akiyama Kosuke, Hirata Naoya, Kitahara Shuji, Maishi Nako, Osawa Takahiro, Yamamoto Kazuyuki, Kondoh Miyako, Shindoh Masanobu, Hida Yasuhiro, Hida Kyoko
発行年月	2012
概要	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.
DOI	10.1371/journal.pone.0034045
PMID	22479517