title: Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Vascular Biology, Graduate School of Dental Medicine, University of Hokkaido, Sapporo, Hokkaido, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ohga
authors.forename: Kosuke
authors.initials: K
authors.lastname: Akiyama
authors.forename: Naoya
authors.initials: N
authors.lastname: Hirata
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitahara
authors.forename: Nako
authors.initials: N
authors.lastname: Maishi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Miyako
authors.initials: M
authors.lastname: Kondoh
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shindoh
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hida
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D002869:Chromosome Aberrations; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D006835:Hydrazones; D009025:Morpholines; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases