Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis

Taisuke Kawamoto, Noritaka Ohga, Kosuke Akiyama, Naoya Hirata, Shuji Kitahara, Nako Maishi, Takahiro Osawa, Kazuyuki Yamamoto, Miyako Kondoh, Masanobu Shindoh, Yasuhiro Hida, Kyoko Hida

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere34045
JournalPloS one
Volume7
Issue number3
DOIs
Publication statusPublished - 30-03-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

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