キタハラ　シュウジ   KITAHARA Shuji
  北原　秀治
   所属   医学研究科 医学研究科 (医学部医学科をご参照ください)
   職種   特任准教授
Article types Original article
Language English
Peer review Peer reviewed
Title Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis.
Journal Formal name：PloS one
Abbreviation：PLoS One
ISSN code：19326203/19326203
Domestic / ForeginForegin
Volume, Issue, Page 7(3),pp.e34045
Author and coauthor Kawamoto Taisuke, Ohga Noritaka, Akiyama Kosuke, Hirata Naoya, Kitahara Shuji, Maishi Nako, Osawa Takahiro, Yamamoto Kazuyuki, Kondoh Miyako, Shindoh Masanobu, Hida Yasuhiro, Hida Kyoko
Publication date 2012
Summary 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