title: Incorporation of naive bone marrow derived cells into the vascular architecture of brain tumor.
abstract: OBJECTIVE
  Neovascularization is essential for tumor growth and invasion. Mounting evidence suggests that tumor cells recruit circulating endothelial progenitor cells to promote vasculogenesis to compliment tumor angiogenesis. This study examines the constitutive role of bone marrow-derived cells in this process.
  
  
  METHODS
  Rat glioma cells were implanted into brains of T-cell-depleted knockout mice. At various timepoints after tumor implantation, naïve bone marrow cells from ubiquitous transgenic mice expressing green fluorescent protein (GFP) were infused into these animals. The incorporation of GFP-positive cells into the vascular architecture was visualized by fluorescence confocal microscopy in conjunction with the transcription profiles of vascular endothelial growth factor (VEGF) and angiopoietin-1 and -2 (Ang-1 and Ang-2).
  
  
  RESULTS
  Of the cells infused, 8 days after tumor implantation, 0.49% were found exclusively sequestered in the vicinity of tumor vessels. This coincided with a decline in the expression of Ang-1 and a rise in the expression of VEGF and Ang-2. A few of these cells (0.66 of the 0.49%) localized onto the vascular wall. They resembled endothelial cells and expressed vWF.
  
  
  CONCLUSIONS
  The incorporation of bone marrow-derived unpurified endothelial cells into the tumor vascular bed is both time-limited and infrequent. These cells may play a supportive rather than a constitutive role in tumor neovascularization.
authors.affiliation: Department of Neurosurgery, Stanford University, California, USA.
authors.forename: Yun C
authors.initials: YC
authors.lastname: Yung
authors.forename: Samuel
authors.initials: S
authors.lastname: Cheshier
authors.forename: Justin G
authors.initials: JG
authors.lastname: Santarelli
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.forename: Amy
authors.initials: A
authors.lastname: Wagers
authors.forename: Irving
authors.initials: I
authors.lastname: Weissman
authors.forename: Victor
authors.initials: V
authors.lastname: Tse
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics; D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D001932:Brain Neoplasms / Q000098:blood supply*; D002465:Cell Movement / Q000502:physiology*; D042783:Endothelial Cells; D020869:Gene Expression Profiling; D005910:Glioma / Q000473:pathology; D049452:Green Fluorescent Proteins; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014183:Transplantation, Heterologous
chemical_list: D042501:Angiogenic Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins